Overcoming Resistance to FLT3 Inhibitors in the Treatment of FLT3-Mutated AML

被引：43

作者：

Lam, Stephen S. Y. ^{[1
]}

Leung, Anskar Y. H. ^{[1
]}

机构：

[1] Univ Hong Kong, Li Ka Shing Fac Med, Div Haematol, Dept Med, Hong Kong, Peoples R China

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2020年 / 21卷 / 04期

关键词：

AML; FLT3; drug resistance; ACUTE MYELOID-LEUKEMIA; KINASE INHIBITOR; CELL TRANSPLANTATION; CLINICAL RESISTANCE; PROMOTES RESISTANCE; MIDOSTAURIN PKC412; PROGNOSTIC IMPACT; TARGETED THERAPY; WILD-TYPE; PHASE-I;

D O I：

10.3390/ijms21041537

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Acute myeloid leukaemia (AML) carrying internal tandem duplication (ITD) of Fms-Like Tyrosine kinase 3 (FLT3) gene is associated with high risk of relapse and poor clinical outcome upon treatment with conventional chemotherapy. FLT3 inhibitors have been approved for the treatment of this AML subtype but leukaemia relapse remains to be a major cause of treatment failure. Mechanisms of drug resistance have been proposed, including evolution of resistant leukaemic clones; adaptive cellular mechanisms and a protective leukaemic microenvironment. These models have provided important leads that may inform design of clinical trials. Clinically, FLT3 inhibitors in combination with conventional chemotherapy as induction treatment for fit patients; with low-intensity treatment as salvage treatment or induction for unfit patients as well as maintenance treatment with FLT3 inhibitors post HSCT hold promise to improve survival in this AML subtype.

引用

页数：13

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