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Entire ABL Gene Is Joined With 5'-BCR In Some Patients With Philadelphia-positive Leukemia

CM Morris, N Heisterkamp, J Groffen, PH Fitzgerald

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In four patients, the chromosome 9 breakpoint of the t(9; 22)(q34;q11) had occurred at different sites within an 8.25-kilobase (kb) region situated 5′ of ABL exon 1B. Chromosome in situ hybridization and field inversion gel electrophoresis (FIGE) studies showed that ABL exons 1A and 1B were present on the Ph chromosome. Yet this large fusion gene produced an mRNA conventional for chronic myelogenous leukemia (CML). Splicing from BCR exon 3 to ABL exon 2 crossed more than 200 kb and deleted exons 1A and 1B. This breakpoint site may occur in about 10% of all CML patients. Three of our patients have pronounced thrombocytosis, and two had been diagnosed as having Ph-positive essential thrombocythemia. The platelet count of the other patient was not available.