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.
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.


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.
Järås
Marcus
M
Department of Clinical Genetics, Lund University, Sweden.
Johnels
Petra
P
Agerstam
Helena
H
Lassen
Carin
C
Rissler
Marianne
M
Edén
Patrik
P
Cammenga
Jörg
J
Olofsson
Tor
T
Bjerrum
Ole Weis
OW
Richter
Johan
J
Fan
Xiaolong
X
Fioretos
Thoas
T
D018952:Antigens, CD34; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D041905:Erythroid Cells / Q000166:cytology*; D005312:Fetal Blood / Q000166:cytology; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000502:physiology*; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D050799:STAT5 Transcription Factor / Q000502:physiology*; D014161:Transduction, Genetic
D018952:Antigens, CD34; D050799:STAT5 Transcription Factor; D016044:Fusion Proteins, bcr-abl