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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

Järås, Marcus LU ; Johnels, Petra LU ; Ågerstam, Helena LU ; Lassen, Carin LU ; Rissler, Marianne LU ; Edén, Patrik LU ; Cammenga, Jörg LU ; Olofsson, Tor LU ; Bjerrum, Ole Weis and Richter, Johan LU , et al. (2009) In Experimental Hematology 37(3). p.367-375
Abstract
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... (More)
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. (Less)
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Experimental Hematology
volume
37
issue
3
pages
367 - 375
publisher
Elsevier
external identifiers
  • wos:000263819200006
  • scopus:59749084821
ISSN
1873-2399
DOI
10.1016/j.exphem.2008.11.003
language
English
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yes
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683af408-7f8f-408a-ab0d-942c4da1f885 (old id 1371163)
date added to LUP
2009-05-08 14:04:04
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2017-01-01 04:54:48
@article{683af408-7f8f-408a-ab0d-942c4da1f885,
  abstract     = {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.},
  author       = {Järås, Marcus and Johnels, Petra and Ågerstam, Helena and Lassen, Carin and Rissler, Marianne and Edén, Patrik and Cammenga, Jörg and Olofsson, Tor and Bjerrum, Ole Weis and Richter, Johan and Fan, Xiaolong and Fioretos, Thoas},
  issn         = {1873-2399},
  language     = {eng},
  number       = {3},
  pages        = {367--375},
  publisher    = {Elsevier},
  series       = {Experimental Hematology},
  title        = {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},
  url          = {http://dx.doi.org/10.1016/j.exphem.2008.11.003},
  volume       = {37},
  year         = {2009},
}