A PHILADELPHIA NEGATIVE CHRONIC MYELOGENOUS LEUKEMIA WITH THE CHIMERIC BCR ABL GENE ON CHROMOSOME-9 AND A B3-A2 SPLICE JUNCTION/

Approximately 5% of patients with chronic myelogenous leukemia (CML) d o not reveal the Philadelphia (Ph) chromosome cytogenetically and are termed Ph-negative Chit cases. We report one such case, which appeared normal by routine banding techniques. The BCR/ABL rearrangement was d etected by reverse transcriptase-polymerase chain reaction and Souther n blotting analysis, which suggested a b3-a2 splice junction. Dual col or fluorescence in situ hybridization (FISH) with BCR and ABL DNA prob es showed that the chimeric fusion gene was localized on chromosome 9q 34, rather than at the typical location on chromosome 22q11. The BCR/A BL rearrangement was detected in 75% of the patient's bone-marrow popu lation, whereas the remaining 25% of the cells appeared normal. The us e of dual color FISH in the diagnosis of CML is extremely valuable not only in identifying cases of Ph-negative CML, but also in quantifying the proportion of transformed cell populations. This information ulti mately results in an enhancement of our ability to monitor therapy, fo llow disease progression, and determine transplant eligibility. (C) El sevier Science Inc., 1998.