Transcriptional analysis of quiescent and proliferating CD34+ human hemopoietic cells from normal and chronic myeloid leukemia sources.
Quiescent and dividing hemopoietic stem cells (HSC) display marked differences in their ability to move between the peripheral circulation and the bone marrow. Specifically, long-term engraftment potential predominantly resides in the quiescent HSC subfraction, and G-CSF mobilization results in the preferential accumulation of quiescent HSC in the periphery. In contrast, stem cells from chronic myeloid leukemia (CML) patients display a constitutive presence in the circulation. To understand the molecular basis for this, we have used microarray technology to analyze the transcriptional differences between dividing and quiescent, normal, and CML-derived CD34+ cells. Our data show a remarkable transcriptional similarity between normal and CML dividing cells, suggesting that the effects of BCR-ABL on the CD34+ cell transcriptome are more limited than previously thought. In addition, we show that quiescent CML cells are more similar to their dividing counterparts than quiescent normal cells are to theirs. We also show these transcriptional differences to be reflected in the altered proliferative activity of normal and CML CD34+ cells. Of the most interest is that the major class of genes that is more abundant in the quiescent cells compared with the dividing cells encodes members of the chemokine family. We propose a role for chemokines expressed by quiescent HSC in the orchestration of CD34+ cell mobilization. Disclosure of potential conflicts of interest is found at the end of this article.
Graham
Susan M
SM
Experimental Haematology, Division of Cancer Sciences, University of Glasgow, Glasgow Royal Infirmary, Glasgow, United Kingdom.
Vass
J Keith
JK
Holyoake
Tessa L
TL
Graham
Gerard J
GJ
D018952:Antigens, CD34 / Q000096:biosynthesis / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D016192:Resting Phase, Cell Cycle / Q000235:genetics*; D014407:Tumor Cells, Cultured
D018952:Antigens, CD34