Mutant FLT3 signaling contributes to a block in myeloid differentiation

@article{Zheng2005MutantFS,
  title={Mutant FLT3 signaling contributes to a block in myeloid differentiation},
  author={Rui Zheng and Donald M. Small},
  journal={Leukemia \& Lymphoma},
  year={2005},
  volume={46},
  pages={1679 - 1687}
}
FLT3 is a member of the class III receptor tyrosine kinase family and is primarily expressed on hematopoietic stem/progenitor cells. Somatic mutations of FLT3 involving internal tandem duplication (ITD) of the juxtamembrane domain or point mutations in the activation loop have been identified in ∼17 – 34% and 7 – 9% of acute myeloid leukemia (AML) patients, respectively. The ITD mutations appear to activate the tyrosine kinase domain through receptor dimerization in a FLT3 ligand-independent… 
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The data suggest that Axl contributes to the pathogenesis of FLT3-ITD(+) AML through, at least in part, positive regulation of constitutiveFLT3 activation.
RUNX1 cooperates with FLT3-ITD to induce leukemia
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It is predicted that blocking RunX1 activity will greatly enhance current therapeutic approaches using FLT3 inhibitors and establish and elucidate the unanticipated oncogenic function of RUNX1 in AML.
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The mechanisms of resistance to FLT3 inhibitors and possible strategies to overcome resistance are discussed through closer examination of the events of leukemogenesis and design of combination therapy.
RUNX1 mutation and elevated FLT3 gene expression cooperates to induce inferior prognosis in cytogenetically normal acute myeloid leukemia patients
NF-κB/STAT5/miR-155 network targets PU.1 in FLT3-ITD-driven acute myeloid leukemia
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A novel network in which FLT3-ITD signaling induces oncogenic miR-155 by p65 and STAT5 in AML, thereby targeting transcription factor PU.1.1, which blocks proliferation and induces apoptosis of FLT 3- ITD-associated leukemic cells.
A Robust Error Model for iTRAQ Quantification Reveals Divergent Signaling between Oncogenic FLT3 Mutants in Acute Myeloid Leukemia*
TLDR
A robust experimental framework and associated error model for iTRAQ-based quantification on an Orbitrap mass spectrometer that relates variance of peptide ratios to mass spectral peak height and provides for assignment of p value, q value, and confidence interval to every peptide identification, obviating the need for detailed characterization of individual ion peaks is described.
Prognostic relevance of FLT3-TKD mutations in AML: the combination matters--an analysis of 3082 patients.
TLDR
An additional favorable impact of FLT3-TKD on EFS in prognostically favorable AML with NPM1- or CEBPA mutations is found and is associated with inferior survival in MLL-PTD/TkD double-mutated cases.
Frequency of FLT3 Internal Tandem Duplications in Adult Syrian Patients with Acute Myeloid Leukemia and Normal Karyotype
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The results support that FLT3-ITD are independent adverse prognostic factors for elderly AML-CN patients and are associated with low overall survival (OS), low rate of CR, high relapse rate (RR), and high percentage of BM blast at diagnosis.
Very late antigen-4 function of myeloblasts correlates with improved overall survival for patients with acute myeloid leukemia.
TLDR
Adhesion and migratory properties of AML blasts thus appear to influence chemosensitivity and therefore may be therapeutic targets.
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