Molecular epidemiology of acute lymphoblastic leukemia in Egypt.
We have characterized immunophenotypically defined acute lymphoblastic leukemia (ALL) in Egypt for rearrangements of the antigen receptor genes, and correlated this with rearrangements of ALL-1 and the presence of p53 mutations. Thirty-nine cases were analyzed for rearrangements of the immunoglobulin (Ig) and T-cell receptor (TCR) genes. All precursor B-cell ALLs (12 cases) contained rearranged Ig heavy-chain (JH) region which was biallelic in 92% of these tumors. In addition to JH rearrangements, TCR delta, beta and gamma rearrangements were observed in 80, 40 and 30% of these cases, respectively. TCR genes were invariably rearranged in T-cell ALLs (11 cases). A small fraction (2/11) of T-cell ALL showed concurrent IgJH rearrangement which was monoallelic. Simultaneous rearrangement of IgJH and TCR genes was also observed in both cases of biphenotypic ALL (coexpressing B and T markers). We observed marked heterogeneity in the pattern of rearrangement of antigen receptor genes in mixed-lineage leukemias (ALL coexpressing myeloid-associated markers), including the retention of germline configuration in two cases. Rearrangements of the ALL-1 gene were confined to the leukemias that demonstrated lineage infidelity. Mutations in p53 were infrequent and were present in only three of 47 ALL cases (6%) analyzed; two of these were mixed-lineage leukemias. These results suggest that mixed-lineage and biphenotypic leukemias accumulate pathogenetic lesions that are distinct from B- and T-cell ALL, and that ALL in developing countries includes molecular entities similar to those in developed countries.
Hamdy
N
N
Pediatric Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Bhatia
K
K
Shaker
H
H
Kamel
A
A
Nazli-Giad-el-Mawla
Abou-Enein
M
M
Yassin
D
D
el-Sharkawy
N
N
Magrath
I
I
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics; D015329:Gene Rearrangement, T-Lymphocyte; D005803:Genes, Immunoglobulin; D016158:Genes, p53; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000276:immunology; D011519:Proto-Oncogenes; D014157:Transcription Factors
D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase