[Detection on BCR-ABL fusion gene in Ph1 chromosome positive leukemia by "nested" retrotranscriptase/polymerase chain reaction].

By using "nested" retrotranscriptase/polymerase chain reaction (RT/PCR) technique, we determined the expression patterns of the BCR-ABL fusion gene resulting from the chromosomal translocation t (9; 22) in leukemias with Ph1 chromosome. Three distinct isoforms of fusion gene transcripts were discovered: ela2, b2a2 and b3a2. In 10 cases of chronic myelogenous leukemia (CML), only two types (b2a2 and b3a2) were observed. However, in 8 cases of Ph1 chromosome positive acute lymphoblastic leukemia (Ph1 + ALL), all three types were detected, including two cases characterized by the coexistence of ela2 and b2a2 or b3a2 types. Moreover, the RT/PCR procedure established in the present study proved to be a very sensitive method, allowing the detection of one leukemic cell among 10(5)-10(6) normal cells. Thus, a positive RT/PCR result was obtained in two Ph1 + ALL cases just after chemotherapy-induced clinical remission (CR), suggesting the presence of residual disease. One case remained RT/PCR positive four months after achieving CR and relapsed in the fifth month, while the other case converted to RT/PCR negative eight months later and is now in CR for 18 months. Therefore the detection of BCR-ABL fusion gene is of importance not only in the study of the pathogenesis of Ph1 + leukemias but also in their diagnosis and monitoring of minimal residual disease during CR.