Molecular Heterogeneity of Adult Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia1

The (9;22) translocation which produces the Philadelphia (Ph1) chro mosome activates the ahi oncogene from chromosome 9 by recombination with the her gene from chromosome 22. This fusion gene is transcribed into a new 8.5-kilobase chimeric niRN A which is translated into a novel M, 210,000 fusion protein which has a protein tyrosine kinase activity that is greatly increased in comparison to the activity of the normal abl protein. Studies from this laboratory and others have shown that virtually all patients with chronic myelogenous leukemia have this new bcrjabl fusion gene. In contrast to these findings in chronic myelogenous leuke mia, a small number of patients with Ph'(+) acute lymphoblastic leuke mia (ALL) have been studied and were found to lack the hcr/ahl fusion gene [bcr(—)],but to have a new activation of abl, by recombination with an as yet undetermined region on chromosome 22. In this study, nine adults with I'h'(+)-AI I, have been examined for evidence of a bcr/abl fusion gene. Of the nine patients, five have a bcr/abl recombination, whereas the remaining four patients do not. In contrast, the children studied to date have all been bcr(—).These data suggest that adults with l"h'(+)-A I.I, are a more heterogeneous group on a molecular level than are children, and that further studies will be required to determine the spectrum of molecular defects in patients with Pii'(+)-AI,l, and the relationship of these various molecular defects to the clinical disease state of the individuals.