MOSAICISM IN BCR-ABL PROTEIN EXPRESSION IN B-CELLS IN CHRONIC MYELOGENOUS LEUKEMIA

Chronic myelogenous leukemia is a disease of the pluripotent stem cell that involves the myeloid and, to a varying degree, the lymphoid comp artment, We studied the involvement of B cells in chronic myelogenous leukemia at diagnosis and during treatment. B lymphocytes were immorta lized by infection with Epstein-Barr virus. B-lymphoid cell lines coul d be established from 25 patients suffering from Philadelphia-chromoso me (Ph(I))-positive chronic myelogenous leukemia. The cell lines were tested for expression of the typical 210-kDa fusion protein, p210, usi ng Western-blot analysis, and/or for mRNA expression of bcr-abl fusion genes, using reverse transcriptase polymerase chain reaction-analysis . At diagnosis, mosaicism of B cells was demonstrated in every patient . During treatment with interferon alpha, p210-expressing B-lymphoid c ell lines could not be established from 8 of 8 patients. Following dis continuation of IFN-alpha therapy, p210-positive cell lines were found early, even before cytogenetic recurrence. Resistance to IFN-alpha th erapy and progression of the disease were both associated with the app earance of p210-positive cell lines. Cell lines established from 3 hea lthy individuals and from patients suffering from Ph(I)-negative disea ses did not show p210 expression in Western Ph involved early in the d isease, and that B-cell mosaicism may be a sensitive marker for resist ance to IFN-alpha-therapy and disease progression. (C) 1996 Wiley-Liss , Inc.