Interleukin (IL)-3/granulocyte macrophage-colony stimulating factor/IL-5 receptor alpha and beta chains are preferentially expressed in acute myeloid leukaemias with mutated FMS-related tyrosine kinase 3 receptor.
The common beta chain subunit (beta(c)), also known as CDw131, shared by the interleukin-3 (IL-3), granulocytic macrophage colony-stimulating factor (GM-CSF) and IL-5 receptors, is required for high-affinity ligand binding and signal transduction. The present study explored the expression of CDw131 in 105 de novo cases of acute myeloid leukaemia (AML). The levels of CDw131 expression were used to identify two AML subgroups characterized by low (75/105) and high (30/105) expression of this receptor chain. It was observed that (i) the level of CDw131 expression strictly correlated with the level of CD116 (GM-CSFalpha receptor chain) and CD123 (IL-3Ralpha chain); (ii) AMLs with high CDw131 expression were characterized by low CD34 expression and usually high CD11b, CD14 expression; (iii) AMLs with high CDw131 expression frequently co-expressed receptors for angiogenic growth factors (vascular endothelial growth factor R2, Tie-2); (iv) AMLs with high CDw131 expression were more cycling than those with low CDw131 expression; (v) AMLs with high CDw131 frequently displayed Feline Murine Sarcoma (FMS-related) tyrosine kinase 3 (FLT3) internal tandem duplication and constitutively activated Signal Transducer and Activator of Transcription-5 (STAT5). In conclusion, the analysis of the level of CDw131 expression enabled the identification of a subset of AMLs characterized by a high cycling status, the expression of myelo-monocytic markers, mutated FLT3 and the co-expression of receptors for angiogenic growth factors. These findings are of value for the development of new therapeutic strategies for the treatment of these AMLs.
Riccioni
Roberta
R
Department of Haematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
Diverio
Daniela
D
Riti
Viviana
V
Buffolino
Sonia
S
Mariani
Gualtiero
G
Boe
Alessandra
A
Cedrone
Michele
M
Ottone
Tiziana
T
Foà
Robin
R
Testa
Ugo
U
D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western / Q000379:methods; D053648:Cytokine Receptor Common beta Subunit / Q000032:analysis* / Q000378:metabolism; D005434:Flow Cytometry; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D016130:Immunophenotyping; D053650:Interleukin-3 Receptor alpha Subunit / Q000032:analysis; D053666:Interleukin-5 Receptor alpha Subunit / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000276:immunology*; D007958:Leukocyte Count; D009154:Mutation; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
D015415:Biomarkers; D053648:Cytokine Receptor Common beta Subunit; D053650:Interleukin-3 Receptor alpha Subunit; D053666:Interleukin-5 Receptor alpha Subunit; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D040301:Vascular Endothelial Growth Factor Receptor-2; D051941:fms-Like Tyrosine Kinase 3