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

ABSTRACT: 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.

SUBMITTER: Lam SSY

PROVIDER: S-EPMC7073218 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Overcoming Resistance to FLT3 Inhibitors in the Treatment of <i>FLT3</i>-Mutated AML.

Lam Stephen S Y SSY Leung Anskar Y H AYH

International journal of molecular sciences 20200224 4

Acute myeloid leukaemia (AML) carrying internal tandem duplication (ITD) of Fms-Like Tyrosine kinase 3 (<i>FLT3</i>) 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 m ...[more]

PMID: 32102366

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