Related Experiment Videos
Human major histocompatibility complex contains several leukemia susceptibility genes
M T Dorak1, E A Chalmers, D Gaffney
1Department of Haematology, University of Wales College of Medicine, Cardiff, UK.
Leukemia & Lymphoma
|January 1, 1994
Summary
Human leukocyte antigen (HLA) homozygosity, particularly for HLA-A3, is linked to early-onset chronic myeloid leukemia (CML). This suggests the human major histocompatibility complex (MHC) influences leukemia development, similar to mouse models.
Area of Science:
- Immunogenetics
- Oncology
Background:
- The mouse Major Histocompatibility Complex (MHC) H-2k haplotype is linked to increased leukemia susceptibility.
- MHC influences malignant development by shortening latency after virus inoculation in mice.
Purpose of the Study:
- To investigate the association between MHC molecular analysis and early-onset human leukemia.
- To explore the role of MHC in the development of chronic myeloid leukemia (CML).
Main Methods:
- Molecular analysis of the MHC in 112 CML patients.
- Comparison of allele and haplotype frequencies between early-onset (<35 years) and late-onset CML groups.
- Statistical analysis to determine relative risk and significance.
Main Results:
- Early-onset CML patients showed higher homozygosity for DOA1, HSP70, and C4 alleles of the DR53 group, a subtype of HLA-A3, and BfFb.
- HLA-A3 homozygosity conferred a high relative risk (17.6) for early-onset CML.
- DR52 haplotypes appeared protective, and HLA-identical sibling frequency was increased in early-onset CML.
Conclusions:
- MHC influences the development of malignancies, including early-onset CML.
- Shared leukemia susceptibility genes between mouse and human MHC are possible, given locus similarity and cross-reactivity.