A late-appearing Philadelphia chromosome in acute lymphoblastic leukemia confirmed by expression of BCR-ABL mRNA

We report two cases of acute lymphoblastic leukemia (ALL) with a late-appearing Philadelphia chromosome (Ph 1 ), confirmed by the expression of BCR-ABL mRNA, using the reverse transcriptase/polymerase chain reaction (RT/PCR) technique. The first patient was a 10-year-old boy with precursor B cell type ALL-L1 (FAB classification). At diagnosis, no metaphase cells were found by chromosome analysis and BCR-ABL mRNA was not observed. At the beginning of relapse, which occurred after 7 months of complete remission, a normal karyotype was observed. At the terminal stage, leukemic cells with Ph 1 and BCR-ABL mRNA for the P190 variety were observed. The second patient was a 12-year-old boy with immature T cell type ALL-L1. The metaphase cells showed a 9p- chromosome at diagnosis and Ph 1 appeared in addition to 9p- at relapse. Hybrid mRNA for the P210 variety was detected only when Ph 1 had developed. The blast cells with Ph 1 were derived from the original leukemic clone through clonal evolution, since the same clonal rearrangements of IGH or TCRB were detected in leukemic cells obtained both at diagnosis and relapse in both patients. Thus, in both cases, Ph 1 was detected only in the course of ALL along with expression of BCR-ABL mRNA. This observation also confirmed that, as in de novo Ph 1 -positive ALL, both the P190 and P210 varieties of BCR-ABL mRNA are observed in ALL with late-appearing Ph 1 . RT/PCR