a Department of Medicine , Penn State Hershey Medical Center , Hershey , PA , USA.
Expert Opin Investig Drugs. 2019 Apr;28(4):337-349. doi: 10.1080/13543784.2019.1584610. Epub 2019 Feb 27.
Tyrosine kinases (TKs) drive cell survival and proliferation in many normal and malignant cell types. TKs are frequently mutated in acute myeloid leukemia (AML) and hence are increasingly targeted. The management of AML has dramatically improved because of TKI-targeted treatment.
This review provides a biological background for TK inhibitors (TKIs) in AML and reviews their use in the clinic. TK expression and mutation in AML are explored with a focus on TKs associated with specific AML subsets and treatment outcomes. TKIs that specifically target FLT3, c-Kit, and Jak2 are discussed. TKI targeting of specific genes mutated in individual cases and general 'untargeted' use of these agents are highlighted. Lastly, the mechanisms TKI drug resistance in AML are explored
The use of TKIs in the clinic is improving outcomes for many patients. An improved understanding of tyrosine kinase biology and the expanding use of TKIs are likely to dramatically improve outcomes in the coming decade. TKIs and other targeted agents could gradually supplant the use of cytotoxic chemotherapy for AML.
酪氨酸激酶（TKs）在许多正常和恶性细胞类型中驱动细胞存活和增殖。TKs 在急性髓系白血病（AML）中经常发生突变，因此越来越多地成为治疗靶点。由于 TKI 靶向治疗，AML 的治疗取得了显著进展。
本文为 AML 中的 TK 抑制剂（TKIs）提供了生物学背景，并综述了其在临床中的应用。本文探讨了 AML 中 TK 的表达和突变，重点关注与特定 AML 亚型和治疗结果相关的 TK。讨论了专门针对 FLT3、c-Kit 和 Jak2 的 TKI。强调了针对个别病例中特定基因突变的 TKI 靶向治疗以及这些药物的一般“无靶向”应用。最后，探讨了 AML 中 TKI 耐药的机制。
TKIs 在临床上的应用改善了许多患者的预后。对酪氨酸激酶生物学的深入了解和 TKI 的广泛应用有望在未来十年内显著改善预后。TKIs 和其他靶向药物可能逐渐取代 AML 中的细胞毒性化疗。
