Detection of trisomy 12 and Rb-deletion in CD34+ cells of patients with
B-cell chronic lymphocytic leukemia
B Gahn, C Schafer, J Neef, C Troff, M Feuring-Buske, W Hiddemann and B Wormann
Department of Hematology and Oncology, University of Gottingen, Germany.
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.
Volume 89,
Issue 12,
pp. 4275-4281,
06/15/1997
Copyright © 1997 by The American Society of Hematology
