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Distinct biological and transcriptional features of FLT3-ITD variants in vitro and in vivo

ABSTRACT: Treatment of FLT3-ITD mutated AML remains a clinical challenge as this subset of patients show high incidence of relapse, even after allogeneic stem cell transplantation. Recently, we defined a molecular subset of FLT3-ITD mutations, located in the FLT3-tyrosine kinase domain 1 (TKD1). In multivariable analyses, insertion of ITD variants in the beta1-sheet (TKD1) was identified as an unfavorable prognostic factor for achievement of a complete remission relapse-free survival and overall survival independently of other prognostic factors such as allelic ratio. In the presented analysis we characterize ITD variants located in the TKD1. While transforming capacity and activation of downstream signaling nodes appears comparable to ‘classical’ ITD mutations located in the JM-domain, TKD1-ITDs reveal a distinct gene expression profile and confer decreased sensitivity to kinase inhibitor therapy in vitro and in vivo. This knowledge may impact clinical decisions in regard to TKI therapy versus allogeneic stem cell transplantation.

ORGANISM(S): Mus musculus

PROVIDER: GSE56241 | GEO | 2014/12/31

SECONDARY ACCESSION(S): PRJNA242713

REPOSITORIES: GEO

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2010-04-08 | E-GEOD-12766 | biostudies-arrayexpress

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de novo childhood AML patients and FLT3 mutations.

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2006-01-06 | E-GEOD-3986 | biostudies-arrayexpress

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