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- Title
MYB-GATA1 fusion promotes basophilic leukaemia: involvement of interleukin-33 and nerve growth factor receptors.
- Authors
Ducassou, Stéphane; Prouzet‐Mauléon, Valérie; Deau, Marie‐Céline; Brunet de la Grange, Philippe; Cardinaud, Bruno; Soueidan, Hayssam; Quelen, Cathy; Brousset, Pierre; Pasquet, Jean‐Max; Moreau‐Gaudry, François; Arock, Michel; Mahon, François‐Xavier; Lippert, Eric
- Abstract
Acute basophilic leukaemia ( ABL) is a rare subtype of acute myeloblastic leukaemia. We previously described a recurrent t(X;6)(p11;q23) translocation generating an MYB-GATA1 fusion gene in male infants with ABL. To better understand its role, the chimeric MYB-GATA1 transcription factor was expressed in CD34-positive haematopoietic progenitors, which were transplanted into immunodeficient mice. Cells expressing MYB-GATA1 showed increased expression of markers of immaturity ( CD34), of granulocytic lineage ( CD33 and CD117), and of basophilic differentiation ( CD203c and FcϵRI). UT-7 cells also showed basophilic differentiation after MYB-GATA1 transfection. A transcriptomic study identified nine genes deregulated by both MYB-GATA1 and basophilic differentiation. Induction of three of these genes ( CCL23, IL1RL1, and NTRK1) was confirmed in MYB-GATA1-expressing CD34-positive cells by reverse transcription quantitative polymerase chain reaction. Interleukin ( IL)-33 and nerve growth factor ( NGF), the ligands of IL-1 receptor-like 1 ( IL1RL1) and neurotrophic receptor tyrosine kinase 1 ( NTRK1), respectively, enhanced the basophilic differentiation of MYB-GATA1-expressing UT-7 cells, thus demonstrating the importance of this pathway in the basophilic differentiation of leukaemic cells and CD34-positive primary cells. Finally, gene reporter assays confirmed that MYB and MYB-GATA1 directly activated NTRK1 and IL1RL1 transcription, leading to basophilic skewing of the blasts. MYB-GATA1 is more efficient than MYB, because of better stability. Our results highlight the role of IL-33 and NGF receptors in the basophilic differentiation of normal and leukaemic cells. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
- Publication
Journal of Pathology, 2017, Vol 242, Issue 3, p347
- ISSN
0022-3417
- Publication type
Article
- DOI
10.1002/path.4908