Detection of trisomy 12 and Rb-deletion in CD34+ cells of patients with B-cell chronic lymphocytic leukemia.
B-cell chronic lymphocytic leukemia (B-CLL) is a slowly progressive disease characterized by the clonal expansion of CD5+/CD23+ B lymphocytes. The malignant transformation is assumed to occur at the level of mature B lymphocytes. We asked whether CD34+ progenitor cells are involved in the malignant process in B-CLL. Furthermore, we investigated the possibility of aberrant CD34 expression by the malignant B-cell clone. Bone marrow and peripheral blood samples from 75 patients with B-CLL were tested for the presence of trisomy 12 and deletion of the retinoblastoma gene (Rb) by fluorescence in situ hybridization. CD34+ subpopulations were isolated by fluorescence-activated cell sorting and analyzed for the presence of the informative genetic marker. Bone marrow and peripheral blood samples of 10 B-CLL patients were analyzed for coexpression of CD34/CD5/CD20. Trisomy 12 was detected in 15 of 75 (20%) and Rb-deletion was detected in 6 of 30 patients (20%). In 7 patients with trisomy 12, hematopoietic progenitor cells were sorted, with the sort purity being between 85% and 99.8%. The genetic marker was detected in the CD34+/CD38+ cells as well as in the CD34+/38- subsets in 3 patients. Progenitor cells were also sorted in 2 patients with Rb-deletion. In 1 patient, Rb-deletion was present in 10% of CD34+/38+ cells. In the other patient, Rb-deletion was neither detected in the CD34+/38+ nor in the CD34+/CD38- subsets. In all 10 patients investigated for coexpression of CD34/CD5/CD20, we could not find a subpopulation coexpressing these markers. We conclude that trisomy 12 and Rb-deletion are present in a considerable subset of patients with B-CLL. In part of these patients, the genetic marker was detected at the level of CD34+ stem cells. CD34 expression is not related to an aberrant phenotype of the malignant B-cell clone. These results suggest that the malignant transformation in B-CLL may involve early hematopoietic stem cells and place a note of caution on future strategies using autologous stem cell transplantation.
Gahn
B
B
Department of Hematology and Oncology, University of Göttingen, Germany.
Schäfer
C
C
Neef
J
J
Troff
C
C
Feuring-Buske
M
M
Hiddemann
W
W
Wörmann
B
B
D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis*; D001402:B-Lymphocytes / Q000648:ultrastructure*; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D016161:Genes, Retinoblastoma; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000648:ultrastructure*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000648:ultrastructure*; D014314:Trisomy
D018952:Antigens, CD34