Evidence for whole chromosome 6 loss and duplication of the remaining chromosome in acute lymphoblastic leukemia.
HLA class I molecules serve the essential immunological function of presenting antigen to CD8+ T lymphocytes. Tumor cells may present tumor-specific antigen to T cells via these molecules, but many tumors show a loss or down-regulation of HLA class I expression and this may serve as an immune escape mechanism. Using a microsatellite marker-based method, we have searched for loss of heterozygosity (LOH) mutations at 3 genomic regions implicated in HLA class I expression in a cohort of 56 acute lymphoblastic leukemia (ALL) samples. The regions analyzed consisted of the HLA class I heavy chain genes located within the MHC genomic region on chromosome arm 6p, the HLA class I light chain (beta-2-microglobulin, B2M) gene on chromosome arm 15q, and the putative HLA modifier of methylation gene (MEMO1) located on chromosome arm 1q. Results revealed low frequencies of B2M (2/55) and MEMO1 (5/42) LOH but a high frequency of MHC LOH (19/56) that was usually associated with whole chromosome 6 loss (13/19). Cytogenetic data were available for 30 samples, including nine of those that exhibited apparent whole chromosome 6 loss. No cases of chromosome 6 monosomy were observed. We propose that whole chromosome 6 loss with reduplication of the remaining chromosome is common in ALL and that it is driven by the presence of tumor-inhibiting factors on chromosome arm 6p (the HLA loci) along with previously localized tumor-suppressor genes on chromosome arm 6q.
McEvoy
Christopher R E
CR
Department of Haematology and Genetic Pathology, Flinders Medical Centre and Flinders University of South Australia, Bedford Park, Australia. chris.mcevoy@flinders.edu.au
Morley
Alexander A
AA
Firgaira
Frank A
FA
D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics; D002648:Child; D002872:Chromosome Deletion; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D015331:Cohort Studies; D020440:Gene Duplication; D006801:Humans; D015448:Leukemia, B-Cell / Q000235:genetics; D015458:Leukemia, T-Cell / Q000235:genetics; D019656:Loss of Heterozygosity / Q000235:genetics; D018895:Microsatellite Repeats / Q000235:genetics; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*
D014408:Biomarkers, Tumor