DETECTION OF BCR-ABL FUSION GENES IN ADULT ACUTE LYMPHOBLASTIC-LEUKEMIA BY THE POLYMERASE CHAIN-REACTION

The sensitivity and clinical utility of the polymerase chain reaction (PCR) assay for the detection of BCR-ABL gene rearrangement was compar ed to conventional cytogenetics for the Philadelphia chromosome (Ph(1) ) in adult acute lymphoblastic leukemia (ALL) patients entered onto a single clinical trial. Ninety-three patients had evaluable PCR assays for both the p190(bcr-abl) and p210(bcr-abl) type of BCR-ABL gene rear rangements. Twenty-one of 93 patients (23%) were positive for the BCR- ABL rearrangement by the PCR assay. Fourteen of these patients had the p210(brc-abl) BCR-ABL rearrangement characteristically seen in CML pa tients, while seven had the p190(brc-abl) rearrangement seen in ALL al one. Of 61 patients analyzed, both with conventional cytogenetics and PCR, eight (13%) were positive for the Ph(1), while 14 (23%) were posi tive for the BCR-ABL rearrangement by the PCR assay. Discordance betwe en the PCR assay and cytogenetics occurred in eight cases where the PC R assay was positive and the cytogenetics negative, and two cases wher e the PCR assay was negative and cytogenetics positive. PCR positivity did not correlate with treatment response, survival, or relapse-free survival, but there was a higher percentage of L2 FAB morphology in th e PCR+ cases compared to the POP-cases (67 vs. 28%, p = 0.003). In add ition, the data suggested that patients with a p190(bcr-abl) rearrange ment have a better response to induction therapy, but a worse relapse- free survival compared to patients with a p210(bcr-abl) breakpoint, bu t these differences were not statistically significant. These data sug gest that PCR and conventional cytogenetics may provide complementary information, since there appear to be a subset of patients who are Phl -negative yet BCR-ABL positive by PCR. Further studies will be require d to determine the prognostic significance of the detailed information about BCR-ABL breakpoints that is available from the PCR assay.