Human major histocompatibility complex contains several leukemia susceptibility genes

Dorak, M. T., Chalmers, E. A., Gaffney, D., Wilson, D. W., Glabraith, I., Henderson, N., Worwood, Mark, Mills, K. I. and Burnett, Alan Kenneth 1994. Human major histocompatibility complex contains several leukemia susceptibility genes. Leukemia and Lymphoma 12 (3-4) , pp. 211-222. 10.3109/10428199409059592

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Abstract

In mice, homozygosity for the Mhc haplotype H-2k is associated with increased susceptibility to spontaneous and virus-induced leukemia, lymphoma and other neoplasms in the predisposed host. The influence of the Mhc on malignant development in these models is to shorten the latency after virus inoculation. Here, we present evidence that a similar phenomenon results in early-onset of human leukemia. A molecular analysis of the MHC in 112 CML patients showed that those who developed the disease when aged less than 35 years (early-onset group) had higher homozygosity rates for the DOA1, HSP70 and C4 alleles of the DR53 group of ancestral haplotypes, for a subtype of HLA-A3, and a higher allele frequency of BfFb compared to the late-onset group. The oldest patient (n = 13) homozygous for DR53 was 52-years-old (p = 0.004), and all HLA-A3 homozygous patients (n = 4) were in the early-onset group (p = 0.01). The relative risk for early-onset CML yielded by HLA-A3 homozygosity was 17.6. The well-known serological HLA-Cw4 association was not confirmed at the DNA level and thought to be due to linkage disequilibrium with BfFb. The factor B association was sex-limited. The DR52 group haplotypes appeared to be protective. The HLA-identical sibling frequency was increased only in the early-onset group (p < 0.01). Our findings agree with the concept of an MHC influence on the development of malignancies. The similarity in the location of the susceptibility loci and the serological cross-reaction between H-2Ek and DR53 raise the possibility that the mouse and human MHC share the same leukemia susceptibility genes.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General) R Medicine > RZ Other systems of medicine
Uncontrolled Keywords:	AcuteDisease,Adolescent,Adult,Aged,Aged80andover,Alleles,CellLine,Child,ChildPreschool,DiseaseSusceptibility/immunology,GeneticPredispositiontoDisease,H2Antigens/genetics*,HLAAAntigens/geneticsHLABAntigens/genetics,HLADAntigens/genetics,Humans,Leukemia/genetics*,Leukemia/immunology*,LeukemiaMyelogenousChronicBCRABLPositive/genetics,LeukemiaMyelogenousChronicBCRABLPositive/immunology,LeukemiaMyeloid/genetics*,LeukemiaMyeloid/immunology*,Lymphoma/genetics,Lymphoma/immunology,Major Histocompatibility Complex*,Middle Aged,Neoplasms/genetics,Neoplasms/immunology,Nuclear Family,Polymorphism Restriction Fragment Length,Restriction Mapping,Tumor Cells, Cultured Substances H-2 Antigens,HLA-A Antigens,HLA-B Antigens,HLA-D Antigens
Additional Information:	Publication Types Research Support, Non-U.S. Gov't Full Text Sources Informa Healthcare Other Literature Sources COS Scholar Universe Medical Childhood Leukemia - MedlinePlus Health Information Leukemia - MedlinePlus Health Information
Publisher:	Informa Healthcare
ISSN:	1042-8194
Last Modified:	25 Jun 2017 04:42
URI:	https://orca.cardiff.ac.uk/id/eprint/59002

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