Transposition of the oncogene ets-1 in t(11;19) translocation in acute leukemia.
The specific chromosomal rearrangement t(11;19)(q23;p13) has been identified as a nonrandom chromosomal rearrangement in acute leukemia. The breakpoint, 11q23, coincides with the ets-1 oncogene locus. However, only very few studies have been done to verify the genomic alteration and transposition of ets-1 in the t(11;19) chromosomal rearrangement. In the present study, we identified the t(11;19)(q23;p13) translocation in two acute leukemic cases. One of the cases, biphenotypic leukemia, has been followed thoroughly. An abnormal karyotype was identified in the patient's blood and marrow samples at diagnosis and at relapse, while only normal karyotypes were identified at remission. In situ hybridization of chromosomal preparations with the ets-1 probe pHE5.4 resulted in silver grains nonrandomly localized to 19p13 in the metaphase spreads prepared from the blood sample taken at relapse, while no detectable grains were found on chromosome 19p13 in a sample taken at remission. To determine if genomic alterations of ets-1 are associated with this translocation, Southern blot hybridizations with the pHE5.4 probe were performed on deoxyribonucleic acid (DNA) isolated from blood or marrow samples of the patient at remission and relapse as well as on DNA from a disease-free normal control. Any DNA digested with AvaII, SstI, XbaI, and Bam HI, followed by hybridization with pHE5.4, demonstrated no genomic alterations or amplification of the ets-1 oncogene. Our study indicates that the ets-1 oncogene is transposed in the t(11;19) translocation without detectable alteration at the DNA level. The absence of ets-1 amplification in t(11;19) and its presence in the t(4,11) and t(9;11) translocations demonstrated by others suggests the possible existence of different molecular mechanisms involving the ets-1 oncogene in the pathogenesis of these leukemias.
Wang
N
N
Department of Pediatrics, University of Rochester School of Medicine, NY 14642.
Cedrone
E
E
Dry
J
J
Skuse
G R
GR
Schwartz
C
C
Terryberry
S
S
D015139:Blotting, Southern; D002648:Child; D002880:Chromosomes, Human, Pair 11; D002888:Chromosomes, Human, Pair 19; D005260:Female; D006801:Humans; D007621:Karyotyping; D007938:Leukemia / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011519:Proto-Oncogenes; D014178:Translocation, Genetic