Biclonal analysis of busulfan-induced sister chromatid exchange in blast crisis of Philadelphia chromosome-positive chronic myeloid leukemia.
The frequency of induced sister chromatid exchange (SCE) as a sensitive parameter for chemotherapy resistance was studied after in vitro treatment with busulfan in four cases of myeloid blast crisis of Philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML). Prerequisite was a chromosomally biclonal condition with cells characterized by numerical and/or structural clonal evolution [e.g., +8, +17, +19, or i(17q)] and those only Ph+, which allowed a direct comparison of both clones. We found almost identical mean SCE frequencies in cells with and without clonal evolution after in vitro treatment with 1, 3, and 5 micrograms busulfan. The distribution of the SCE frequency within chromosome groups also remained similar in all cases. Because the SCE assay has proven a very sensitive tool for detection of resistance to chemotherapy with alkylating agents, we conclude that the clonal evolution of CML blast crisis is not associated with a significant degree of chemotherapy resistance. Other aspects, e.g., the lack of normal bone marrow cells necessary for reconstitution of hematopoiesis, may play a more important role in the poor results of chemotherapy in myeloid CML blast crisis.
Becher
R
R
Innere Universitäts- und Poliklinik (Tumorforschung), Universitätsklinikum Essen, F.R.G.
Prescher
G
G
D001752:Blast Crisis / Q000235:genetics*; D002066:Busulfan / Q000494:pharmacology*; D002453:Cell Cycle; D004171:Diploidy; D004351:Drug Resistance / Q000235:genetics; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008677:Metaphase; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D002066:Busulfan