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FLT3 - 版本历史
2026-04-18T16:36:04Z
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2026年1月23日 (五) 09:31 77921020
2026-01-23T09:31:36Z
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">←上一版本</td>
<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">2026年1月23日 (五) 09:31的版本</td>
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<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> [Image:FLT3_receptor_structure_signaling.png|100px|FLT3 受体结构与信号传导]</div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <ins class="diffchange diffchange-inline">[</ins>[Image:FLT3_receptor_structure_signaling.png|100px|FLT3 受体结构与信号传导<ins class="diffchange diffchange-inline">]</ins>]</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </div></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </div></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">AML 核心驱动 / RTK III型</div></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">AML 核心驱动 / RTK III型</div></div></td></tr>
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<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <ul style="padding-left: 25px; color: #334155;"></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <ul style="padding-left: 25px; color: #334155;"></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <li style="margin-bottom: 12px;"><strong><del class="diffchange diffchange-inline">继发突变 (Secondary Mutations)：</del></strong></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <li style="margin-bottom: 12px;"><strong><ins class="diffchange diffchange-inline">继发性激酶突变：</ins></strong></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <br><del class="diffchange diffchange-inline">• <strong></del>D835 <del class="diffchange diffchange-inline">突变：</strong> 如果使用 II 型抑制剂（奎扎替尼）后出现，可换用 <strong></del>I <del class="diffchange diffchange-inline">型抑制剂</strong>（如吉瑞替尼）。</del></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <br><ins class="diffchange diffchange-inline">使用 II 型抑制剂（奎扎替尼）后，常见 </ins>D835 <ins class="diffchange diffchange-inline">突变涌现。使用 </ins>I <ins class="diffchange diffchange-inline">型抑制剂（吉瑞替尼）后，可能出现“看门人”突变 </ins><strong>[[<ins class="diffchange diffchange-inline">F691L</ins>]]</strong><ins class="diffchange diffchange-inline">，该突变阻碍了药物的结合，目前仍是临床难点。</ins></li></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del class="diffchange diffchange-inline"> <br>• <strong>F691L 突变：</strong> 被称为“泛耐药”突变，对吉瑞替尼和奎扎替尼均不敏感。</del><strong>[[<del class="diffchange diffchange-inline">Crenolanib</del>]]</strong> <del class="diffchange diffchange-inline">是目前临床试验中对 F691L 有效的下一代 I 型抑制剂。</del></li></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <li style="margin-bottom: 12px;"><strong><ins class="diffchange diffchange-inline">旁路激活：</ins></strong></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <li style="margin-bottom: 12px;"><strong><del class="diffchange diffchange-inline">旁路激活 (Bypass Pathways)：</del></strong></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <br><ins class="diffchange diffchange-inline">肿瘤细胞可能通过激活 RAS</ins>/<ins class="diffchange diffchange-inline">MAPK 或上调其他激酶（如 </ins>[[<ins class="diffchange diffchange-inline">AXL</ins>]]<ins class="diffchange diffchange-inline">）来绕过 FLT3 抑制。联合使用 </ins>BCL-<ins class="diffchange diffchange-inline">2 抑制剂（</ins>[[<ins class="diffchange diffchange-inline">维奈克拉</ins>]]<ins class="diffchange diffchange-inline">）是目前克服耐药的主要策略。</ins></li></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <br><del class="diffchange diffchange-inline">肿瘤细胞可能绕过 FLT3，通过上调 BCL-2、RAS 或 AXL 来存活。</del></div></td><td colspan="2"> </td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del class="diffchange diffchange-inline"> <br><strong>解决方案：<</del>/<del class="diffchange diffchange-inline">strong> 联合用药是关键。<strong></del>[[<del class="diffchange diffchange-inline">吉瑞替尼</del>]] <del class="diffchange diffchange-inline">+ [[维奈克拉]]</strong> (Venetoclax, </del>BCL-<del class="diffchange diffchange-inline">2i) 组合在复发难治患者中显示出极高的协同致死效应。此外，联合去甲基化药物（HMA）或化疗也是标准策略。</li></del></div></td><td colspan="2"> </td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del class="diffchange diffchange-inline"> <li style="margin-bottom: 12px;"><strong>终极手段：</strong></del></div></td><td colspan="2"> </td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del class="diffchange diffchange-inline"> <br><strong></del>[[<del class="diffchange diffchange-inline">异基因造血干细胞移植</del>]]<del class="diffchange diffchange-inline"></strong> (allo-HSCT) 仍然是 FLT3 突变 AML 唯一可能的治愈手段。TKI 药物常作为移植前的“桥接”治疗或移植后的维持治疗以降低复发。</del></li></div></td><td colspan="2"> </td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </ul></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </ul></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
<tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l138" >第138行：</td>
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<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> [1] <strong><del class="diffchange diffchange-inline">Perl AE</del>, <del class="diffchange diffchange-inline">Martinelli G</del>, <del class="diffchange diffchange-inline">Cortes JE</del>, et al. (<del class="diffchange diffchange-inline">2019</del>).</strong> <em><del class="diffchange diffchange-inline">Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML</del>.</em> <strong>[[<del class="diffchange diffchange-inline">New England Journal of Medicine</del>]]</strong>. <del class="diffchange diffchange-inline">2019</del>;<del class="diffchange diffchange-inline">381</del>(<del class="diffchange diffchange-inline">18</del>):<del class="diffchange diffchange-inline">1728</del>-<del class="diffchange diffchange-inline">1740</del>.<br></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> [1] <strong><ins class="diffchange diffchange-inline">Nakao M</ins>, <ins class="diffchange diffchange-inline">Yokota S</ins>, <ins class="diffchange diffchange-inline">Iwai T</ins>, et al. (<ins class="diffchange diffchange-inline">1996</ins>).</strong> <em><ins class="diffchange diffchange-inline">Internal tandem duplication of the flt3 gene found in acute myeloid leukemia</ins>.</em> <strong>[[<ins class="diffchange diffchange-inline">Leukemia</ins>]]</strong>. <ins class="diffchange diffchange-inline">1996</ins>;<ins class="diffchange diffchange-inline">10</ins>(<ins class="diffchange diffchange-inline">12</ins>):<ins class="diffchange diffchange-inline">1911</ins>-<ins class="diffchange diffchange-inline">1918</ins>.<br></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <span style="color: #475569;">[学术点评]<del class="diffchange diffchange-inline">：ADMIRAL 研究。确立了吉瑞替尼作为复发/难治性 </del>FLT3 <del class="diffchange diffchange-inline">突变 </del>AML <del class="diffchange diffchange-inline">的新标准治疗，证明单药治疗优于挽救性化疗，且对 ITD 和 TKD 突变均有效。</del></span></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <span style="color: #475569;">[学术点评]<ins class="diffchange diffchange-inline">：发现之源。首次报道了 </ins>FLT3<ins class="diffchange diffchange-inline">-ITD 突变，揭示了 </ins>AML <ins class="diffchange diffchange-inline">中这一最常见且具有预后意义的分子异常，奠定了后续靶向治疗的基础。</ins></span></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </p></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </p></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> [2] <strong><del class="diffchange diffchange-inline">Erba HP</del>, <del class="diffchange diffchange-inline">Montesinos P</del>, <del class="diffchange diffchange-inline">Kim HJ</del>, et al. (<del class="diffchange diffchange-inline">2023</del>).</strong> <em><del class="diffchange diffchange-inline">Quizartinib </del>plus <del class="diffchange diffchange-inline">chemotherapy in newly diagnosed patients </del>with FLT3<del class="diffchange diffchange-inline">-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trial</del>.</em> <strong>[[<del class="diffchange diffchange-inline">The Lancet</del>]]</strong>. <del class="diffchange diffchange-inline">2023</del>;<del class="diffchange diffchange-inline">401</del>(<del class="diffchange diffchange-inline">10388</del>):<del class="diffchange diffchange-inline">1571</del>-<del class="diffchange diffchange-inline">1583</del>.<br></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> [2] <strong><ins class="diffchange diffchange-inline">Stone RM</ins>, <ins class="diffchange diffchange-inline">Mandrekar SJ</ins>, <ins class="diffchange diffchange-inline">Sanford BL</ins>, et al. (<ins class="diffchange diffchange-inline">2017</ins>).</strong> <em><ins class="diffchange diffchange-inline">Midostaurin </ins>plus <ins class="diffchange diffchange-inline">Chemotherapy for Acute Myeloid Leukemia </ins>with <ins class="diffchange diffchange-inline">a </ins>FLT3 <ins class="diffchange diffchange-inline">Mutation</ins>.</em> <strong>[[<ins class="diffchange diffchange-inline">New England Journal of Medicine</ins>]]</strong>. <ins class="diffchange diffchange-inline">2017</ins>;<ins class="diffchange diffchange-inline">377</ins>(<ins class="diffchange diffchange-inline">5</ins>):<ins class="diffchange diffchange-inline">454</ins>-<ins class="diffchange diffchange-inline">464</ins>.<br></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <span style="color: #475569;">[学术点评]<del class="diffchange diffchange-inline">：QuANTUM-First 研究。证实了第二代 II 型抑制剂奎扎替尼在一线治疗中的生存获益。但也提示了其局限性：由于不覆盖 TKD 突变，复发时常伴随 D835 突变的出现。</del></span></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <span style="color: #475569;">[学术点评]<ins class="diffchange diffchange-inline">：RATIFY 研究。具有里程碑意义的 III 期试验，证实米多斯莫联合化疗可显著延长 FLT3 突变 AML 患者的总生存期，促成了首个 FLT3 抑制剂的获批。</ins></span></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </p></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </p></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> [3] <strong><del class="diffchange diffchange-inline">Smith CC</del>, <del class="diffchange diffchange-inline">Levis MJ</del>, <del class="diffchange diffchange-inline">Perl AE</del>, et al. (<del class="diffchange diffchange-inline">2018</del>).</strong> <em><del class="diffchange diffchange-inline">Molecular Profile </del>of FLT3-<del class="diffchange diffchange-inline">Mutated Acute Myeloid Leukemia Patients </del>with <del class="diffchange diffchange-inline">Relapse after Targeted Therapy</del>.</em> <strong>[[<del class="diffchange diffchange-inline">Blood</del>]]</strong>. <del class="diffchange diffchange-inline">2018</del>;<del class="diffchange diffchange-inline">132</del>(<del class="diffchange diffchange-inline">Supplement 1</del>):<del class="diffchange diffchange-inline">147</del>.<br></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> [3] <strong><ins class="diffchange diffchange-inline">Perl AE, Martinelli G, Cortes JE, et al. (2019).</strong> <em>Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML.</em> <strong>[[New England Journal of Medicine]]</strong>. 2019;381(18):1728-1740.<br></ins></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <span style="color: #475569;">[学术点评]<del class="diffchange diffchange-inline">：耐药机制。深入分析了 I 型和 </del>II <del class="diffchange diffchange-inline">型抑制剂治疗后的复发模式，明确指出了 </del>F691L <del class="diffchange diffchange-inline">是 I 型抑制剂的软肋，而 D835 是 II 型抑制剂的软肋，为临床换药提供了分子依据。</del></span></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> <span style="color: #475569;">[学术点评]：ADMIRAL 研究。确立了第二代 I 型抑制剂吉瑞替尼作为复发/难治性 FLT3 突变 AML 的新标准治疗，证明单药治疗优于挽救性化疗，且对 ITD 和 TKD 突变均有效。</span></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> </p></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> </div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> <p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> [4] <strong>Döhner H</ins>, <ins class="diffchange diffchange-inline">Wei AH</ins>, <ins class="diffchange diffchange-inline">Appelbaum FR</ins>, et al. (<ins class="diffchange diffchange-inline">2022</ins>).</strong> <em><ins class="diffchange diffchange-inline">Diagnosis and management </ins>of <ins class="diffchange diffchange-inline">AML in adults: 2022 recommendations from an international expert panel.</em> <strong>[[Blood]]</strong>. 2022;140(12):1345-1377.<br></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> <span style="color: #475569;">[学术点评]：权威指南。ELN 2022 指南更新了 </ins>FLT3-<ins class="diffchange diffchange-inline">ITD 的预后分层标准，引入了等位基因比 (AR) 的概念，并建议在高危患者中尽早使用靶向药物和考虑移植。</span></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> </p></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> </div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> <p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> [5] <strong>Erba HP, Montesinos P, Kim HJ, et al. (2023).</strong> <em>Quizartinib plus chemotherapy in newly diagnosed patients </ins>with <ins class="diffchange diffchange-inline">FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trial</ins>.</em> <strong>[[<ins class="diffchange diffchange-inline">The Lancet</ins>]]</strong>. <ins class="diffchange diffchange-inline">2023</ins>;<ins class="diffchange diffchange-inline">401</ins>(<ins class="diffchange diffchange-inline">10388</ins>):<ins class="diffchange diffchange-inline">1571-1583</ins>.<br></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <span style="color: #475569;">[学术点评]<ins class="diffchange diffchange-inline">：QuANTUM-First 研究。证实了第二代 </ins>II <ins class="diffchange diffchange-inline">型抑制剂奎扎替尼在一线治疗中的生存获益，特别是对 ITD 突变患者的强效抑制，但其对 TKD 无效及心脏毒性需关注。</span></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> </p></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> </div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> <p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> [6] <strong>Smith CC, Wang Q, Chin CS, et al. (2012).</strong> <em>Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukemia.</em> <strong>[[Nature]]</strong>. 2012;485(7397):260-263.<br></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> <span style="color: #475569;">[学术点评]：耐药机制。该研究系统性地阐明了 FLT3 抑制剂治疗后的继发性耐药机制，特别是确定了 </ins>F691L <ins class="diffchange diffchange-inline">作为“看门人”突变，为新一代药物（如 Crenolanib）的研发指明了方向。</span></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> </p></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> </div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> <p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> [7] <strong>Daver N, Schlenk RF, Russell NH, et al. (2019).</strong> <em>Targeting FLT3 mutations in AML: review of current knowledge and evidence.</em> <strong>[[Leukemia]]</strong>. 2019;33(2):299-312.<br></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> <span style="color: #475569;">[学术点评]：综合综述。全面总结了 FLT3 抑制剂的临床应用、耐药机制及联合治疗策略（如与化疗、低甲基化药物、BCL-2 抑制剂的联用），是理解 FLT3 治疗全貌的必读文献。</ins></span></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </p></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </p></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </div></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </div></div></td></tr>
<tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l160" >第160行：</td>
<td colspan="2" class="diff-lineno">第176行：</td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <tr style="border-bottom: 1px solid #f1f5f9;"></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <tr style="border-bottom: 1px solid #f1f5f9;"></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">突变亚型</td></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">突变亚型</td></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 10px 15px; color: #334155;">[[FLT3-ITD]] (高负荷预后差) • [[FLT3-TKD]] (D835) • [[F691L]] (<del class="diffchange diffchange-inline">难治</del>)</td></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 10px 15px; color: #334155;">[[FLT3-ITD]] (高负荷预后差) • [[FLT3-TKD]] (D835) • [[F691L]] (<ins class="diffchange diffchange-inline">耐药</ins>)</td></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </tr></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </tr></div></td></tr>
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77921020：建立内容为“<div style="padding: 0 4%; line-height: 1.8; color: #1e293b; font-family: 'Helvetica Neue', Helvetica, 'PingFang SC', Arial, sans-serif; background-color: #ffffff…”的新页面
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<p>建立内容为“<div style="padding: 0 4%; line-height: 1.8; color: #1e293b; font-family: 'Helvetica Neue', Helvetica, 'PingFang SC', Arial, sans-serif; background-color: #ffffff…”的新页面</p>
<p><b>新页面</b></p><div><div style="padding: 0 4%; line-height: 1.8; color: #1e293b; font-family: 'Helvetica Neue', Helvetica, 'PingFang SC', Arial, sans-serif; background-color: #ffffff; max-width: 1200px; margin: auto;"><br />
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<strong>FLT3</strong>（Fms-Like Tyrosine Kinase 3），全称为 <strong>Fms 样酪氨酸激酶 3</strong>，属于 III 型受体酪氨酸激酶（RTK）家族。正常情况下，FLT3 主要表达于造血干/祖细胞表面，与配体（FLT3 Ligand）结合后，调控血细胞的生存、增殖和分化。然而，在 <strong>[[急性髓系白血病]] (AML)</strong> 中，FLT3 是突变频率最高的基因（约占 30%）。其突变会导致激酶持续性自主活化，驱动白血病细胞的爆发式增殖。临床上，FLT3 突变状态（特别是 <strong>[[FLT3-ITD]]</strong>）是 AML 极为重要的<strong>预后不良因子</strong>，也是指导造血干细胞移植和靶向药物使用的核心生物标志物。<br />
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<div style="font-size: 1.25em; font-weight: bold; letter-spacing: 1.2px;">FLT3 · 基因档案</div><br />
<div style="font-size: 0.75em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Gene & Protein Comprehensive Profile (点击展开)</div><br />
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[[文件:Protein_FLT3_Structure_PDB.png|110px|FLT3 胞外域结构示意图]]<br />
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<div style="font-size: 0.85em; color: #64748b; margin-top: 15px; font-weight: 600;">III 型受体酪氨酸激酶</div><br />
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<th style="text-align: left; padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc; width: 40%;">基因全名</th><br />
<td style="padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">Fms-Related Receptor Tyrosine Kinase 3</td><br />
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<th style="text-align: left; padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">基因符号</th><br />
<td style="padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #0f172a;"><strong>FLT3</strong></td><br />
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<th style="text-align: left; padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">常用别名</th><br />
<td style="padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">CD135, FLK2, STK1</td><br />
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<th style="text-align: left; padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">染色体位置</th><br />
<td style="padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">13q12.2</td><br />
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<th style="text-align: left; padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">生物分类</th><br />
<td style="padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #0f172a;"><em>Homo sapiens</em> (智人)</td><br />
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<th style="text-align: left; padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">Entrez Gene</th><br />
<td style="padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #1e40af;">2322</td><br />
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<th style="text-align: left; padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">HGNC ID</th><br />
<td style="padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #1e40af;">3765</td><br />
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<th style="text-align: left; padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">OMIM</th><br />
<td style="padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #1e40af;">136351</td><br />
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<th style="text-align: left; padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">UniProt</th><br />
<td style="padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #1e40af;">P36888</td><br />
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<th style="text-align: left; padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">蛋白类型</th><br />
<td style="padding: 8px 15px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">受体酪氨酸激酶 (RTK)</td><br />
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<th style="text-align: left; padding: 8px 15px; color: #475569; background-color: #f8fafc;">分子量</th><br />
<td style="padding: 8px 15px; color: #0f172a;">~130-160 kDa</td><br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">致病机制：刹车失灵的激酶</h2><br />
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<p style="margin: 15px 0; text-align: justify;"><br />
FLT3 的致癌机制通常涉及“自身抑制”功能的丧失。正常情况下，近膜结构域（JMD）像一个“刹车”一样抑制激酶活性。当发生突变时，这种抑制被解除，导致 <strong>[[STAT5]]</strong>、<strong>[[RAS/MAPK]]</strong> 和 <strong>PI3K/AKT</strong> 通路的组成性激活。<br />
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<ul style="padding-left: 25px; color: #334155;"><br />
<li style="margin-bottom: 12px;"><strong>ITD 突变 (Internal Tandem Duplication)：</strong> 发生在 JMD 区域的内部串联重复。这是最常见的变异，直接破坏了 JMD 的负调控构象，导致激酶持续活跃。ITD 的长度和插入位点与预后相关。</li><br />
<li style="margin-bottom: 12px;"><strong>TKD 突变 (Tyrosine Kinase Domain)：</strong> 主要是 <strong>D835</strong> 位点的点突变，位于激酶活化环（Activation Loop），使激酶被锁定在开放的活性构象。</li><br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">临床景观：ITD 与 TKD 的分野</h2><br />
<p style="margin: 15px 0; text-align: justify;"><br />
在 AML 的诊疗中，FLT3 的突变检测是初诊时的必选项。不同的突变类型对预后分层（Prognostic Stratification）有着截然不同的影响。<br />
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<th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">突变亚型</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">发生频率 (AML)</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">临床意义与预后</th><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">FLT3-ITD</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>~25%</strong></td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">高白细胞计数，高复发率，<strong>预后不良</strong>。高 AR 值（等位基因比）提示更高风险，通常建议在缓解后尽快进行异基因造血干细胞移植（allo-HSCT）。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">FLT3-TKD (D835)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">~5-10%</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">对预后的影响尚存争议，一般被认为是<strong>中等预后</strong>。常作为耐药突变在复发时出现。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">耐药突变 (如 F691L)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">复发时常见</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">“看门人突变”。由于改变了 ATP 结合口袋构象，对 I 型抑制剂（如吉瑞替尼）产生耐药。</td><br />
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</table><br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">靶向治疗：从米多到吉瑞</h2><br />
<p style="margin: 15px 0; text-align: justify;"><br />
FLT3 抑制剂的研发显著改善了 FLT3 突变型 AML 患者的生存。药物主要分为两代，治疗策略常包含“诱导期联用”和“移植后维持”：<br />
</p><br />
<ul style="padding-left: 25px; color: #334155;"><br />
<li style="margin-bottom: 12px;"><strong>第一代（多激酶抑制剂）：</strong> <br />
<ul style="margin-top: 5px;"><br />
<li><strong>[[米多石印]]</strong> (Midostaurin/Rydapt)：首个获批药物。与“7+3”化疗联用是一线治疗标准（RATIFY 研究）。特异性较低，副作用（如胃肠道反应）较多。</li><br />
<li><strong>[[索拉非尼]]</strong> (Sorafenib)：常用于移植后维持治疗。</li><br />
</ul><br />
</li><br />
<li style="margin-bottom: 12px;"><strong>第二代（高选择性抑制剂）：</strong><br />
<ul style="margin-top: 5px;"><br />
<li><strong>[[吉瑞替尼]]</strong> (Gilteritinib/Xospata)：单药用于治疗复发/难治性（R/R）AML。是目前的“金标准”，能同时抑制 ITD 和 TKD 突变。</li><br />
<li><strong>[[奎扎替尼]]</strong> (Quizartinib)：对 ITD 突变抑制效力极强，但对 TKD 无效。需注意 QT 间期延长风险。</li><br />
</ul><br />
</li><br />
</ul><br />
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<div style="font-size: 0.92em; line-height: 1.6; color: #1e293b; margin-top: 50px; border-top: 2px solid #0f172a; padding: 15px 25px; background-color: #f8fafc; border-radius: 0 0 10px 10px;"><br />
<span style="color: #0f172a; font-weight: bold; font-size: 1.05em; display: inline-block; margin-bottom: 15px;">学术参考文献与权威点评</span><br />
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<p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"><br />
[1] <strong>Nakao M, et al. (1996).</strong> <em>Internal tandem duplication of the flt3 gene found in acute myeloid leukemia.</em> <strong>Leukemia</strong>. <br><br />
<span style="color: #475569;">[学术点评]：开创性发现，首次鉴定出 FLT3-ITD 突变，并揭示了其与 AML 高白细胞计数和不良预后的关联。</span><br />
</p><br />
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<p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"><br />
[2] <strong>Stone RM, et al. (2017).</strong> <em>Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation.</em> <strong>New England Journal of Medicine</strong>. <br><br />
<span style="color: #475569;">[学术点评]：RATIFY 研究，证实了米多石印联合化疗能显著延长初诊 FLT3 突变 AML 患者的总生存期，确立了一线标准。</span><br />
</p><br />
<br />
<p style="margin: 12px 0;"><br />
[3] <strong>Perl AE, et al. (2019).</strong> <em>Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML.</em> <strong>New England Journal of Medicine</strong>. <br><br />
<span style="color: #475569;">[学术点评]：ADMIRAL 研究，证明了二代药物吉瑞替尼单药治疗 R/R AML 优于挽救性化疗，成为复发患者的首选。</span><br />
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<div style="margin: 40px 0; border: 1.5px solid #0f172a; border-radius: 8px; overflow: hidden; font-size: 0.95em;"><br />
<div style="background-color: #0f172a; color: #ffffff; text-align: center; font-weight: bold; padding: 10px; letter-spacing: 1px;">FLT3 · 知识图谱关联</div><br />
<div style="padding: 15px; background: #ffffff; line-height: 2.2; text-align: center; text-decoration: none;"><br />
[[急性髓系白血病]] • [[FLT3-ITD]] • [[吉瑞替尼]] • [[米多石印]] • [[造血干细胞移植]] • [[NPM1]] • [[D835突变]]<br />
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