DETECTION AND CLINICAL RELEVANCE OF GENETIC ABNORMALITIES IN PEDIATRIC ACUTE LYMPHOBLASTIC-LEUKEMIA - A COMPARISON BETWEEN CYTOGENETIC AND POLYMERASE CHAIN-REACTION ANALYSES

The E2A/PBX1 and the BCR/ABL fusion genes result from the t(1;19)(q23; p13) and the t(9;22)(q34;q11), respectively, and encode oncoproteins w hich are thought to play an important role in the development of acute lymphoblastic leukemia (ALL) subtypes associated with adverse prognos is. The use of the polymerase chain reaction (PCR) for the detection o f these genetic rearrangements may offer advantages over cytogenetic t echniques which are often unsatisfactory in patients with ALL and, fur thermore, provide a useful tool for monitoring of residual disease. Ho wever, it has not yet been evaluated whether the employment of PCR at the time of diagnosis improves the detection rate of these clinically relevant genetic anomalies. We have developed a multiprimer-PCR protoc ol which facilitates the detection of each of the four chimeric E2A/PB X1 and BCR/ABL mRNAs in a single reaction. This protocol was used for the evaluation of bone-marrow or blood samples from 251 children with ALL in whom cytogenetic analyses had been performed. Of the 251 patien ts, 221 had a B-cell precursor immunophenotype. In this group, 21 pati ents (9.5%) carrying the E2A/PBX1 rearrangement and three patients (1. 4%) with BCR/ABL transcripts were detected by PCR. Twelve of these cas es had escaped the detection by conventional cytogenetic analysis. In two of 12 patients with a typical t(1;19)(q23;p13), no E2A/PBX1 transc ripts were identified by PCR, thus suggesting the presence of differen t molecular rearrangements. Residual leukemic cells were detected by P CR in five of eight patients who were followed during complete clinica l remission. The frontline use of PCR has an important impact on the t imely diagnosis, therapeutic decisions, and monitoring of high-risk pa tients with B-cell precursor leukemia who carry the E2A/PBX1 or BCR/AB L fusion genes.