UNUSUAL EXPRESSION OF MESSENGER-RNA TYPICAL OF PHILADELPHIA-POSITIVE ACUTE LYMPHOBLASTIC-LEUKEMIA DETECTED IN CHRONIC MYELOID-LEUKEMIA

The Philadelphia chromosome (Ph) is found in both chronic myeloid leuk emia (CML) andacute lymphoblastic leukemia (ALL). The Ph translocation , t(9;22)(q34;q11), can disrupt the BCR gene on chromosome 22 in one t o two areas called the major (Mbcr1) and minor (mbcr1) breakpoint clus ter regions. In CML the breakpoint has been mapped almost exclusively to Mbcr1, whereas in Ph positive ALL both Mbcr1 and the upstream mbcr1 breakpoints have been described. In this communication we describe an unusual patient with typical chronic phase Ph positive CML and eviden ce of the uncharacteristic mbcr1 breakpoint, predicting expression of the ALL-type p190 fusion protein, Fluorescence in situ hybridization d emonstrated BCR gene rearrangement, the reverse transcription polymera se chain reaction detected the BCR-ABL fusion mRNA characteristic of t he mbcr1 breakpoint, and failed to detect BCR-ABL mRNA characteristic of the Mbcr1 breakpoint. Southern blot analysis revealed no rearrangem ent in Mbcr1, and direct sequencing of the PCR product confirmed it to be the ALL-type mbcr1 fusion mRNA with the first exon of the BCR gene fused to ABL exon a2. This case differs from the previously reported cases of ''p190'' CML in that the patient presented without abnormal h ematopoietic features other than those found in typical CML and provid es further evidence that the p190 mRNA is not sufficient to cause an a cute rather than chronic leukemia. (C) 1996 Wiley-Liss, Inc.