BCR/ABL- CD34+HLA-DR- progenitor cells in early chronic phase, but not in more advanced phases, of chronic myelogenous leukemia are polyclonal

被引:18
作者
Delforge, M
Boogaerts, MA
McGlave, PB
Verfaillie, CM
机构
[1] Univ Hosp Gasthuisberg, Dept Med, Div Hematol, B-3000 Louvain, Belgium
[2] Univ Minnesota, Dept Med, Div Hematol, Minneapolis, MN 55455 USA
关键词
D O I
10.1182/blood.V93.1.284.401k31_284_292
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 a-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 a re norm at. 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. (C) 1999 by The American Society of Hematology.
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页码:284 / 292
页数:9
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