Cancer Institute A national cancer institute
designated cancer center

Michael Link

Publication Details

  • SIMULTANEOUS EXPRESSION OF RBTN-2 AND BCR-ABL ONCOGENES IN A T-ALL WITH A T(1114)(P13Q11) AND A LATE-APPEARING PHILADELPHIA-CHROMOSOME LEUKEMIA Fizzotti, M., CHEN, E. Y., Link, M. P., Carroll, A. J., Foroni, L., Rabbitts, T. H., Crist, W. M., Clark, S. S. 1994; 8 (7): 1124-1130

    Abstract:

    Cytogenetic analysis of a pediatric patient with T-cell acute lymphoblastic leukemia (T-ALL) revealed a mosaic karyotype, 47,XX,+17,t(11;14)(p13;q11)/47,XX,+17,t(9;22)(q34;q11),t(11;14) (p13;q11). DNA blot analysis was used to examine the break-point within the BCR gene on chromosome 22 and showed that the breakpoint occurred within the 20-kb minor breakpoint cluster region (m-bcr) located within the first intron of the BCR gene. Immunoprecipitation analysis demonstrated that the leukemic cells expressed the P185 BCR-ABL protein tyrosine kinase. P185 BCR-ABL has previously been shown to be expressed in most cases of Ph+ acute leukemia of 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 hybridization was also used to characterize the t(11;14) translocation. This showed rearrangement on chromosome 11 within the T-ALLbcr region, upstream of the RBTN-2 gene. Polymerase chain reaction revealed the presence of RBTN-2 transcripts in the leukemic cells. Finally, comparison of the T-ALLbcr, BCR-ABL, IGH, TCR beta and gamma gene rearrangements in leukemic cells obtained at the time of diagnosis and at first relapse showed that relapse occurred in a leukemic clone indistinguishable from the major Ph+ clone involved at diagnosis. Together, these 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 carried these abnormalities.

    View details for Web of Science ID A1994NZ72300006

    View details for PubMedID 8035604

Stanford Medicine Resources:

Footer Links: