Analysis of progenitor cell involvement in B-CLL by simultaneous immunophenotypic and genotypic analysis at the single cell level

B-cell chronic lymphocytic leukaemia (B-CLL) results from the clonal expans ion of mature B lymphocytes. The detection of leukaemia-associated genetic markers in CD34-positive progenitor cells in a subset of B-CEL patients sug gests that malignant transformation in B-CLL occurs in an immature progenit or cell compartment. To further quantify the percentage of B-CLL patients w ith genetically aberrant progenitor cells we have investigated CD34(+) bone marrow cells in 11 B-CU patients at the single cell level by simultaneous genetic and immunophenotypic analysis (FICTION). In five patients with tris omy 12, CD34(+) haemopoietic progenitor cells were detectable on bone marro w smears. In one patient with trisomy 12, CD34+ progenitor cells were isola ted by FAGS sorting. In all six patients trisomy 12 was not found in the CD 34(+) cells. Progenitor cells were also analysed in three patients with Rb- deletion and in two patients with deletion of p53. In all patients the gene tic marker was not detected in the CD34(+) cells. In conclusion, we did not find genetically aberrant progenitor cells in this group of B-CLL patients . These results suggest that the subset of B-CU patients with genetically a berrant CD34(+) cells may be very small. This is of significance for our un derstanding of B-CLL biology and for future strategies using autologous ste m cell transplantation.