SIMULTANEOUS EXPRESSION OF RBTN-2 AND BCR-ABL ONCOGENES IN A T-ALL WITH A T(1114)(P13911) AND A LATE-APPEARING PHILADELPHIA-CHROMOSOME

Cytogenetic analysis of a pediatric patient with T-cell acute lymphobl astic leukemia (T-ALL) revealed a mosaic karyotype, 1;14)(p13;q11)/47, XX,+17,t(9;22)(q34;q11),t(11;14) (p13;q11). DNA blot analysis was used to examine the breakpoint within the BCR gene on chromosome 22 and sh owed that the breakpoint occurred within the 20-kb minor breakpoint cl uster region (m-bcr) located within the first intron of the BCR gene. Immunoprecipitation analysis demonstrated that the leukemic cells expr essed the P185 BCR-ABL protein tyrosine kinase. P185 BCR-ABL has previ ously been shown to be expressed in most cases of Ph+ acute leukemia o f myeloid and B-progenitor origin. Here, we demonstrate for the first time that P185 can also be expressed in the T-cell lineage. DNA blot h ybridization was also used to characterize the t(11;14) translocation. This showed rearrangement on chromosome 11 within the T-ALL(bcr) regi on, upstream of the RBTN-2 gene. Polymerase chain reaction revealed th e presence of RBTN-2 transcripts in the leukemic cells. Finally, compa rison of the T-ALL(bcr), BCR-ABL, IGH, TCR beta and gamma gene rearran gements in leukemic cells obtained at the time of diagnosis and at fir st relapse showed that relapse occurred in a leukemic clone indistingu ishable from the major Ph+ clone involved at diagnosis. Together, thes e data support a multistep pathogenesis in which the Philadelphia (Ph) chromosome translocation appeared subsequent to the +17 and t(11,14) and imparted a growth advantage over the Ph-negative cells that carrie d these abnormalities.