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Thoas Fioretos

Thoas Fioretos

Research team manager

Thoas Fioretos

Expression of P190 and P210 BCR/ABL1 in normal human CD34(+) cells induces similar gene expression profiles and results in a STAT5-dependent expansion of the erythroid lineage

Author

  • Marcus Järås
  • Petra Johnels
  • Helena Ågerstam
  • Carin Lassen
  • Marianne Rissler
  • Patrik Edén
  • Jörg Cammenga
  • Tor Olofsson
  • Ole Weis Bjerrum
  • Johan Richter
  • Xiaolong Fan
  • Thoas Fioretos
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Summary, in English

Objective. The P190 and P210 BCR/ABL1 fusion genes are mainly associated with different types of hematologic malignancies, but it is presently unclear whether they are functionally different following expression in primitive human hematopoietic cells. Materials and Methods. We investigated and systematically compared the effects of retroviral P190 BCR/ABL1 and P210 BCR/ABL1 expression on cell proliferation, differentiation, and global gene expression in human CD34(+) cells from cord blood. Results. Expression of either P190 BCR/ABL1 or P210 BCR/ABL1 resulted in expansion of erythroid cells and stimulated erythropoietin-independent burst-forming unit-erythroid colony formation. By using a lentiviral anti-signal transducer and activator of transcription 5 (STAT5) short-hairpin RNA, we found that both P190 BCR/ABL1- and P210 BCR/ABL1-induced erythroid cell expansion were STAT5-dependent. Under in vitro conditions favoring B-cell differentiation, neither P190 nor P210 BCR/ABL1-expressing cells formed detectable levels of CD19-positive cells. Gene expression profiling revealed that P190 BCR/ABL1 and P210 BCR/ABL1 induced almost identical gene expression profiles. Conclusions. Our data suggest that the early cellular and transcriptional effects of P190 BCR/ABL1 and P210 BCR/ABL1 expression are very similar when they are expressed in the same human progenitor cell population, and that STAT5 is an important regulator of BCR/ABL1-induced erythroid cell expansion. (C) 2009 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.

Department/s

  • Division of Clinical Genetics
  • Division of Molecular Medicine and Gene Therapy
  • Computational Biology and Biological Physics - Has been reorganised
  • Stem Cell Center
  • Division of Hematology and Transfusion Medicine

Publishing year

2009

Language

English

Pages

367-375

Publication/Series

Experimental Hematology

Volume

37

Issue

3

Document type

Journal article

Publisher

Elsevier

Topic

  • Hematology

Status

Published

ISBN/ISSN/Other

  • ISSN: 1873-2399