Impaired S-Phase Arrest in Acute Myeloid Leukemia Cells with a FLT3 Internal Tandem Duplication Treated with Clofarabine

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Impaired S-phase arrest in acute myeloid leukemia cells with a FLT3 internal tandem duplication treated with clofarabine.

PURPOSE Acute myeloid leukemia cells with an internal tandem duplication mutation of FLT3 (FLT3-ITD) have effective DNA repair mechanisms on exposure to drugs. Despite this, the phenotype is not associated with primary resistant disease. We show defects in the response of mutant FLT3 AML cells to the S-phase drug clofarabine that could account for the apparent contradiction. EXPERIMENTAL DESI...

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Cancer Therapy: Preclinical Impaired S-Phase Arrest in Acute Myeloid Leukemia Cells with a FLT3 Internal Tandem Duplication Treated with Clofarabine

Purpose: Acute myeloid leukemia cells with an internal tandem duplication mutation of FLT3 (FLT3-ITD) have effective DNA repair mechanisms on exposure to drugs. Despite this, the phenotype is not associated with primary resistant disease. We show defects in the response of mutant FLT3 AML cells to the S-phase drug clofarabine that could account for the apparent contradiction. Experimental Desig...

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Immunophenotypic findings in acute myeloid leukemia with FLT3 internal tandem duplication.

BACKGROUND AND OBJECTIVES The biological characteristics and the prognostic significance of the internal tandem duplication of the FLT3 (FLT3/ITD) were investigated in a series of de novo acute myeloid leukemia (AML) patients. One hundred and fifty-six adult patients with AML were included in the study. FLT3/ITD was detected in 41 (26%) patients (FLT3/ITD(+)). DESIGN AND METHODS The main diff...

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Size of FLT3 internal tandem duplication has prognostic significance in patients with acute myeloid leukemia.

FLT3 internal tandem duplications (FLT3/ITDs) in the juxtamembrane domain are found in approximately 25% of acute myeloid leukemia (AML) patients, ranging in size from 3 to hundreds of nucleotides. We examined whether the sizes of FLT3/ITDs were associated with clinical outcomes in 151 AML patients enrolled in Southwest Oncology Group studies: S9333 and S9500. FLT3/ITDs were identified in 32% o...

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Characteristics and Prognosis of Adult Acute Myeloid Leukemia with Internal Tandem Duplication in the FLT3 Gene.

OBJECTIVES Constitutive activation of the fms-like tyrosine kinase 3 (FLT3) receptor by internal tandem duplication (ITD) of the juxtamembrane region has been described in patients with acute myeloid leukemia. FLT3/ITDs are present in about 20-30% of all acute myeloid leukemia cases. It has been shown that the mutation is correlated with worse prognosis. However, none of the previous studies in...

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ژورنال

عنوان ژورنال: Clinical Cancer Research

سال: 2009

ISSN: 1078-0432,1557-3265

DOI: 10.1158/1078-0432.ccr-09-1222