Identification of a germline F692L drug resistance variant in cis with Flt3-internal tandem duplication in knock-in mice
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چکیده
منابع مشابه
FLT3 internal tandem duplication in 234 children with acute myeloid leukemia: prognostic significance and relation to cellular drug resistance.
FLT3 is a receptor tyrosine kinase involved in the proliferation and differentiation of hematopoietic stem cells. FLT3 internal tandem duplications (FLT3/ITDs) are reported in acute myeloid leukemia (AML) and predict poor clinical outcome. We found FLT3/ITDs in 11.5% of 234 children with de novo AML. FLT3/ITD-positive patients were significantly older and had higher percentages of normal cytoge...
متن کاملKnock-in of an internal tandem duplication mutation into murine FLT3 confers myeloproliferative disease in a mouse model.
Constitutive activation of FMS-like tyrosine kinase 3 (FLT3) by internal tandem duplication (ITD) mutations is one of the most common molecular alterations known in acute myeloid leukemia (AML). To investigate the role FLT3/ITD mutations play in the development of leukemia, we generated a FLT3/ITD knock-in mouse model by inserting an ITD mutation into the juxtamembrane domain of murine Flt3. FL...
متن کاملMll partial tandem duplication and Flt3 internal tandem duplication in a double knock-in mouse recapitulates features of counterpart human acute myeloid leukemias.
The MLL-partial tandem duplication (PTD) associates with high-risk cytogenetically normal acute myeloid leukemia (AML). Concurrent presence of FLT3-internal tandem duplication (ITD) is observed in 25% of patients with MLL-PTD AML. However, mice expressing either Mll-PTD or Flt3-ITD do not develop AML, suggesting that 2 mutations are necessary for the AML phenotype. Thus, we generated a mouse ex...
متن کاملSize 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...
متن کاملCharacteristics 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: Haematologica
سال: 2016
ISSN: 0390-6078,1592-8721
DOI: 10.3324/haematol.2016.146159