Immunophenotypic features of acute myeloid leukaemia patients exhibiting high FLT3 expression not associated with mutations
- 20 February 2011
- journal article
- Published by Wiley in British Journal of Haematology
- Vol. 153 (1), 33-42
- https://doi.org/10.1111/j.1365-2141.2011.08577.x
Abstract
FMS-related tyrosine kinase 3 (FLT3) mutations are found in 30% of cases of acute myeloid leukaemia (AML). In addition, recent studies have lead to the identification of about 10-15% of AML patients displaying high expression of FLT3, not associated with mutations of the receptor (FLT3 Wild-type High, FLT3WTH). These AMLs, as well as those displaying internal tandem duplication (ITD) are associated with an unfavourable prognosis. However, the biological features of these AMLs are poorly characterized. The present study explored the immunophenotypic features of FLT3WTH AMLs in 94 de novo cases of AML. The levels of FLT3 expression, as assessed by flow cytometry and FLT3 mutational status, was used to identify four AML subgroups: FLT3WTH (14/94); FLT3 Wild-type low (FLT3WTL, 48/94); FLT3 internal tandem duplication (FLT3ITD 26/94); FLT3 aspartic acid 835 (FLT3D835, 6/94). FLT3WTH and FLT3ITD were characterized by: high white blast cell counts; predominance of M4 and M5 French-American-British classification subtypes and associated expression of myelo-monocytic markers; high expression of CD123 and TRAIL-Rs; high expression of receptors for angiogenic growth factors. Addition of FLT3 Ligand to human CD34(+) or monocytic cells stimulated CD123 and TRAIL-R expression. These findings are of potential value for the development of new therapeutic strategiesThis publication has 37 references indexed in Scilit:
- High Transcript Level of FLT3 Associated with High Risk of Relapse in Pediatric Acute Myeloid LeukemiaJournal of Korean Medical Science, 2010
- Leukaemogenesis: more than mutant genesNature Reviews Cancer, 2010
- VEGF/KDR loop is a target of AG1296 in acute myeloid leukaemia showing FLT3-internal tandem duplicationsBritish Journal of Haematology, 2009
- FLT3 D835/I836 mutations are associated with poor disease-free survival and a distinct gene-expression signature among younger adults with de novo cytogenetically normal acute myeloid leukemia lacking FLT3 internal tandem duplicationsBlood, 2008
- Critical role of FLT3 ligand in IL-7 receptor–independent T lymphopoiesis and regulation of lymphoid-primed multipotent progenitorsBlood, 2007
- Expression of Tie-2 and Other Receptors for Endothelial Growth Factors in Acute Myeloid Leukemias Is Associated with Monocytic Features of Leukemic BlastsThe International Journal of Cell Cloning, 2007
- Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: are we ready for a prognostically prioritized molecular classification?Blood, 2006
- Diphtheria toxin fused to variant human interleukin-3 induces cytotoxicity of blasts from patients with acute myeloid leukemia according to the level of interleukin-3 receptor expressionBlood, 2005
- Immunophenotypic Features of Acute Myeloid Leukemias Overexpressing the Interleukin 3 Receptor Alpha ChainLeukemia & Lymphoma, 2004
- A receptor tyrosine kinase specific to hematopoietic stem and progenitor cell-enriched populationsCell, 1991