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BCR/ABL− CD34+HLA-DR−Progenitor Cells in Early Chronic Phase, But Not in More Advanced Phases, of Chronic Myelogenous Leukemia Are Polyclonal
- Source :
- Scopus-Elsevier
- Publication Year :
- 1999
- Publisher :
- American Society of Hematology, 1999.
-
Abstract
- Chronic myelogenous leukemia (CML) is characterized by the Philadelphia (Ph) translocation and BCR/ABL gene rearrangement which occur in a pluripotent hematopoietic progenitor cell. Ph-negative (Ph-) hematopoiesis can be restored in vivo after treatment with -interferon or intensive chemotherapy, suggesting that normal stem and progenitor cells coexist with the Ph+ clone. We have previously shown that Ph- progenitors are highly enriched in the CD34(+)HLA-DR- fraction from early chronic phase (ECP) CML patients. Previous studies have suggested that the Ph-translocation represents a secondary clonal hit occurring in an already clonally mutated Ph- progenitor or stem cells, leaving the unanswered question whether Ph- CD34(+)HLA-DR- progenitors are normal. To show the clonal nature of Ph- CD34(+)HLA-DR- CML progenitors, we have compared the expression of BCR/ABL mRNA with X-chromosome inactivation patterns (HUMARA) in mononuclear cells and in CD34(+)HLA-DR+ and CD34(+)HLA-DR- progenitors in marrow and blood obtained from 11 female CML patients (8 in chronic phase and 3 in accelerated phase [AP] disease). Steady-state marrow-derived BCR/ABL mRNA-, CD34(+)HLA-DR- progenitors had polyclonal X-chromosome inactivation patterns in 2 of 2 patients. The same polyclonal pattern was found in the progeny of CD34(+)HLA-DR- derived long-term culture-initiating cells. Mobilization with intensive chemotherapy induced a Ph-, BCR/ABL mRNA- and polyclonal state in the CD34(+)HLA-DR- and CD34(+)HLA-DR+ progenitors from 2 ECP patients. In a third ECP patient, polyclonal CD34(+) cells could only be found in the first peripheral blood collection. In contrast to ECP CML, steady-state marrow progenitors in late chronic phase and AP disease were mostly Ph+, BCR/ABL mRNA+, and clonal. Further, in the majority of these patients, a Ph-, polyclonal state could not be restored despite mobilization with intensive chemotherapy. We conclude from these studies that CD34(+)HLA-DR- cells that are Ph- and BCR/ABL mRNA- are polyclonal and therefore benign. This population is suitable for autografting in CML. ispartof: Blood vol:93 issue:1 pages:284-92 ispartof: location:United States status: published
- Subjects :
- Adult
Time Factors
Immunology
CD34
Fusion Proteins, bcr-abl
Antigens, CD34
Bone Marrow Cells
Biology
Genes, abl
Polymerase Chain Reaction
Biochemistry
hemic and lymphatic diseases
medicine
Humans
Progenitor cell
Cells, Cultured
ABL
breakpoint cluster region
HLA-DR Antigens
Cell Biology
Hematology
medicine.disease
Hematopoietic Stem Cells
Clone Cells
Leukemia
Haematopoiesis
Leukemia, Myeloid
Cancer research
Female
Stem cell
Chronic myelogenous leukemia
Subjects
Details
- ISSN :
- 15280020 and 00064971
- Volume :
- 93
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....64aa338dde6f04a2b183015660d14ac0