Internal Tandem Duplication (ITD) in the Tyrosine Kinase Domain of FLT3 Displays Higher Oncogenic Potential in Acute Myeloid Leukemia

A FLT3 tyrosine kinase inhibitor is selectively cytotoxic to acute myeloid leukemia blasts harboring FLT3 internal tandem duplication mutations.

Internal tandem duplication (ITD) mutations of the receptor tyrosine kinase FLT3 have been found in 20% to 30% of patients with acute myeloid leukemia (AML). These mutations constitutively activate the receptor and appear to be associated with a poor prognosis. Recent evidence that this constitutive activation is leukemogenic renders this receptor a potential target for specific therapy. In thi...

Cooperation between the partial tandem duplication of Mll (Mll PTD) and internal tandem duplication of FLT3 (FLT3 ITD) in the pathogenesis of acute myeloid leukemia (AML)

fms like tyrosine kinase3- internal tandem duplication (flt3-itd) in acute myeloid leukemia, mutation frequency and its relation with complete remission, 2007- 2008

introduction: about half of acute myeloid leukemia (aml) adult patients have no cytogenetic abnormalities as a main determinant of complete remission after treatment, so other markers are needed such as flt3-itd (fms-like tyrosine kinase3-internal tandem duplication) mutations in patients with normal karyotype. the objective of this study was assessing the frequency of flt3-itd mutations and it...

Pim kinases modulate resistance to FLT3 tyrosine kinase inhibitors in FLT3-ITD acute myeloid leukemia

Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) is frequently detected in acute myeloid leukemia (AML) patients and is associated with a dismal long-term prognosis. FLT3 tyrosine kinase inhibitors provide short-term disease control, but relapse invariably occurs within months. Pim protein kinases are oncogenic FLT3-ITD targets expressed in AML cells. We show that increased Pim...

Activating internal tandem duplication mutations of the fms-like tyrosine kinase-3 (FLT3-ITD) at complete response and relapse in patients with acute myeloid leukemia.

FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutations are among the most frequent molecular aberrations in patients with acute myeloid leukemia. We retrospectively analyzed 324 patients with acute myeloid leukemia treated with front-line induction chemotherapy between October 2004 and March 2010. Fifty-six patients had FLT3-ITD mutation at diagnosis. Fifty-one (91%) patien...