Close association of aberrant CD7 expression and FLT3/ITD mutation in the myeloblasts of FLT3/ITD+ AML suggests that FLT3/ITD- mediated leukemic transformation occurs in the more early stage of myeloid progenitor cells.
Thus, the distribution of Flt3 expression is considerably different in human and mouse hematopoiesis, and human FLT3 signaling might play an important role in cell survival, especially at stem and progenitor cells that are critical cellular targets for acute myelogenous leukemia transformation.
We retrospectively analysed the prevalence of NPM1 and Flt3-ITD mutations and its association with complete remission (CR), and survival in 99 elderly patients (median age 71 yr, range 60-85 yr) newly diagnosed for AML.
Blockade of MEK/ERK signaling enhances sunitinib-induced growth inhibition and apoptosis of leukemia cells possessing activating mutations of the FLT3 gene.
The FLT3 internal tandem duplication (ITD) and the D835 activating mutation in the tyrosine kinase domain (TKD) were analyzed by polymerase chain reaction (PCR) in the genomic DNA of Korean patients with AML at diagnosis and during follow-up.
These associations with outcome, other prognostic markers, and the elucidated expression signature enhance our understanding of FLT3-TKD-associated biology and may lead to development of novel therapies that improve clinical outcome of CN-AML patients with FLT3-TKD.
These data show that activated FLT3 cooperates with MLL-AF9 to accelerate onset of an AML from whole bone marrow as well as a committed hematopoietic progenitor, and provide a new genetically defined model system that should prove useful for rapid assessment of potential therapeutics in vivo.
In this study, Southeast Asian AML patients with a favorable karyotype including t(8;21)/AML-ETO, inv(16)(CBF beta/SMMHC), and t(15;17)/PML-RAR alpha were genotyped for KIT and FLT3 RTK mutations by PCR and sequencing.
These results support the hypothesis that Flt3-mediated signaling in AML enables accumulation of Bcl-2 and maintains a downstream block to p53 pathway apoptosis.
To resolve this issue we screened 1107 young adult nonacute promyelocytic leukemia AML patients with known FLT3 internal tandem duplication (ITD) status for FLT3/TKDs; they were detected in 127 (11%) cases.
Quantitation of FLT3 transcript levels revealed a highly significant (P < .001) about 5-fold increase in AML with RUNX1 mutations and trisomy 13 compared with samples without trisomy 13.
Several large-scale studies in well-documented patients published to date have demonstrated that FLT3 mutations are strongly associated with a poor prognosis and a high leukemia cell count in patients with AML, suggesting that FLT3 mutations are involved in disease progression.
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.
Heterogeneous patterns of FLT3 Asp(835) mutations in relapsed de novo acute myeloid leukemia: a comparative analysis of 120 paired diagnostic and relapse bone marrow samples.
We have investigated the presence of FLT3-ITD and D835 mutations in AML patients and their correlation with clinical and biological disease characteristics.