Abstract
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. © 2003 Wiley‐Liss, Inc.