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.
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.
Department of Human Oncology, University of Wisconsin, Madison 53792.
M
M
Fizzotti
E Y
EY
Chen
M P
MP
Link
A J
AJ
Carroll
L
L
Foroni
T H
TH
Rabbitts
W M
WM
Crist
S S
SS
Clark
D001483:Base Sequence; D002648:Child; D002880:Chromosomes, Human, Pair 11; D002883:Chromosomes, Human, Pair 14; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins; D005260:Female; D015870:Gene Expression; D016313:Genes, abl; D006801:Humans; D015151:Immunoblotting; D016130:Immunophenotyping; D007621:Karyotyping; D060588:LIM Domain Proteins; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D008969:Molecular Sequence Data; D015513:Oncogene Proteins; D010677:Philadelphia Chromosome; D012334:RNA, Neoplasm / Q000032:analysis; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C065072:LMO1 protein, human; D015513:Oncogene Proteins; D012334:RNA, Neoplasm; D014157:Transcription Factors