DETECTION OF TRISOMY-12 AND RB-DELETION IN CD34(-CELL CHRONIC LYMPHOCYTIC-LEUKEMIA() CELLS OF PATIENTS WITH B)

chronic lymphocytic leukemia (B-CLL) is a slowly progressive disease c haracterized by the clonal expansion of CD5(+)/CD23(+) B lymphocytes, The malignant transformation is assumed to occur at the level of matur e B lymphocytes. We asked whether CD34(+) progenitor cells are involve d 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 retinob lastoma gene (Rb) by fluorescence in situ hybridization. CD34(+) subpo pulations were isolated by fluorescence-activated cell sorting and ana lyzed for the presence of the informative genetic marker. Bone marrow and peripheral blood samples of 10 B-CLL patients were analyzed for co expression 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 detec ted in the CD34(+)/CD38(+) cells as well as in the CD34(+)/38(-) subse ts 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 patie nts investigated for coexpression of CD34/CD5/CD20, we could not find a subpopulation coexpressing these markers. We conclude that trisomy 1 2 and Rb-deletion are present in a considerable subset of patients wit h 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 sugge st that the malignant transformation in B-CLL may involve early hemato poietic stem cells and place a note of caution on future strategies us ing autologous stem cell transplantation. (C) 1997 by The American Soc iety of Hematology.