Simultaneous expression of RBTN-2 and BCR-ABL oncogenes in a T-ALL with a t(11;14)(p13;q11) and a late-appearing Philadelphia chromosome

Academic Article

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 breakpoint 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-ALL(bcr) 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-ALL(bcr), BCR-ABL, IGH, TCRβ and γ 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.
  • Author List

  • Fizzotti M; Chen EY; Link MP; Carroll AJ; Foroni L; Rabbitts TH; Crist WM; Clark SS
  • Start Page

  • 1124
  • End Page

  • 1130
  • Volume

  • 8
  • Issue

  • 7