title: Immunophenotypic features of acute myeloid leukaemia patients exhibiting high FLT3 expression not associated with mutations.
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 strategies.
authors.affiliation: Department of Haematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Riccioni
authors.forename: Elvira
authors.initials: E
authors.lastname: Pelosi
authors.forename: Viviana
authors.initials: V
authors.lastname: Riti
authors.forename: Germana
authors.initials: G
authors.lastname: Castelli
authors.forename: Francesco
authors.initials: F
authors.lastname: Lo-Coco
authors.forename: Ugo
authors.initials: U
authors.lastname: Testa
mesh_terms: D018952:Antigens, CD34 / Q000032:analysis; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016130:Immunophenotyping; D053650:Interleukin-3 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008565:Membrane Proteins / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009154:Mutation; D042787:Receptor, TIE-2 / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014407:Tumor Cells, Cultured; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics / Q000378:metabolism*
chemical_list: D018952:Antigens, CD34; C115022:IL3RA protein, human; D053650:Interleukin-3 Receptor alpha Subunit; D008565:Membrane Proteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; C084881:flt3 ligand protein; C497970:FLT3 protein, human; D042787:Receptor, TIE-2; D040301:Vascular Endothelial Growth Factor Receptor-2; D051941:fms-Like Tyrosine Kinase 3