Targeting FLT3 for the treatment of leukemia.
Targeting FLT3 for the treatment of leukemia.
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DOI：
10.1053/j.seminhematol.2008.07.007
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发表时间：
2008-07
影响因子：
3.6
通讯作者：
Small D
中科院分区：
文献类型：
--
作者：
Small D
FLT 3是一种受体酪氨酸激酶，在造血干/祖细胞存活和增殖中具有重要作用。它在急性白血病中经常过表达，并且在急性髓性白血病（AML）中经常突变。AML中的FLT 3内部串联重复（ITD）突变预示着成人和儿童患者的预后不良。已经发现了许多对FLT 3具有活性的小分子酪氨酸激酶抑制剂（TKI）。其中许多药物仍处于临床前开发阶段，但有几种药物已进入临床1期和2期试验，作为复发性AML患者的单药治疗。这些试验导致外周原始细胞的频繁但短暂的应答，而骨髓原始细胞的应答频率较低。这导致了FLT 3 TKI与常规化疗联合的临床试验。正在进行或计划在复发和新诊断的FLT 3突变AML患者中进行几项联合试验。抗FLT 3抗体也可能被证明是一种通过抑制信号传导和抗体依赖性细胞介导的细胞毒性靶向AML和急性淋巴细胞白血病（ALL）中FLT 3的极好方法。
FLT3 is a receptor tyrosine kinase with important roles in hematopoietic stem/progenitor cell survival and proliferation. It is frequently overexpressed in acute leukemias and is frequently mutated in acute myeloid leukemia (AML). FLT3 internal tandem duplication (ITD) mutations in AML portend poor prognosis in both adult and pediatric patients. A number of small molecule tyrosine kinase inhibitors (TKIs) with activity against FLT3 have been discovered. Many of these are still in preclinical development, but several have entered clinical phase 1 and 2 trials as monotherapy in patients with relapsed AML. These trials have resulted in frequent but short-lived responses of peripheral blasts and less frequent responses of bone marrow blasts. This led to clinical testing of FLT3 TKIs in combination with conventional chemotherapy. Several combination trials are ongoing or planned in both relapsed and newly diagnosed FLT3-mutant AML patients. Anti-FLT3 antibodies may also prove to be an excellent way of targeting FLT3 in AML and acute lymphocytic leukemia (ALL) by inhibiting signaling and through antibody-dependent cell-mediated cytotoxicity.
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