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 ge nes, 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 precur sor B-cell ALLs (12 cases) contained rearranged Ig heavy-chain (JH) re gion which was biallelic in 92% of these tumors. In addition to JH rea rrangements, TCR delta, beta and gamma rearrangements were observed in 80, 40 and 30% of these cases, respectively. TCR genes were invariabl y rearranged in T-cell ALLs (11 cases). A small fraction (2/11) of T-c ell ALL showed concurrent IgJH rearrangement which was monoallelic. Si multaneous rearrangement of IgJH and ICR genes was also observed in bo th cases of biphenotypic ALL (coexpressing B and T markers). We observ ed marked heterogeneity in the pattern of rearrangement of antigen rec eptor genes in mixed-lineage leukemias (ALL coexpressing myeloid-assoc iated markers), including the retention of germline configuration in t wo cases. Rearrangements of the ALL-1 gene were confined to the leukem ias that demonstrated lineage infidelity. Mutations in p53 were infreq uent and were present in only three of 47 ALL cases (6%) analyzed; two of these were mixed-lineage leukemias. These results suggest that mix ed-lineage and biphenotypic leukemias accumulate pathogenetic lesions that are distinct from B- and T-cell ALL, and that ALL in developing c ountries includes molecular entities similar to those in developed cou ntries.