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HLA system affects the age-at-onset in chronic myeloid leukemia

Lookup NU author(s): Dr Tevfik Dorak


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Chronic myeloid leukemia (CML) occurs from childhood to old age. The adult form is characterized by the presence of Philadelphia chromosome resulting from bcr/abl translocation. The BCR-ABL fusion proteins are immunogenic, and the junctional sequences show unique HLA class I and class II restriction patterns in vitro. A previous study in the west of Scotland showed an influence of several HLA genotypes on the age-at-onset of CML. In the present study, we examined the HLA-A, -B, and -DRB1/3/4/5 allele and haplotype distributions in Turkish CML patients diagnosed in a single center where they are routinely HLA-typed by PCR-SSP analysis as a preparation for stem cell transplantation. The patients were 169 subjects of age 17-60 years. The older patients were not HLA typed and missing from the study group. The age-matched control group (n = 213) was healthy blood donors from the same geographical area. HLA-B*37 showed a risk association with CML [P = 0.02; odds ratio (OR) = 5.35]. The DRB1*10 association at similar magnitude was due to its linkage disequilibrium (LD) with B*37. HLA-B*35 and DRB1*11 showed independent protective effects (P = 0.007 and 0.017; OR = 0.54 and 0.60, respectively). The protective association of DRB1*11 may be due to its involvement in the presentation of the common (b3a2) fusion gene. HLA-B*14 and DRB1*01 showed strong LD, and all 5 patients who were positive for the presumed haplotype B*14-DRB1*01 were of age 43 years old or older (P = 0.003), suggesting a delay effect. We also examined the influence of homozygosity for DRB3 (DR52) and DRB4 (DR53) haplotypes on susceptibility. As previously shown in CML and CLL, DRB4 homozygosity was a risk marker (P = 0.01; OR = 3.36), and DRB3 homozygosity was protective (P = 0.007; OR = 0.51). Despite the lack of elderly patients in the study group, the opposite accelerating (DRB4) and delaying (DRB3) effects of homozygous genotypes on the age-at-onset were evident. Besides replicating previously found associations in a different population, this study also suggested new, and probably population-specific associations in CML. The mechanisms by which the HLA system modifies susceptibility to CML are unknown, likely to include immune and nonimmune ones, and worthy of further studies.

Publication metadata

Author(s): Dorak MT; Oguz FS; Kalayoglu S; Diler AS; Tozkir H; Sargin D; Carin M

Publication type: Article

Publication status: Published

Journal: American Journal of Hematology

Year: 2003

Volume: 73

Issue: 4

Pages: 256-262

ISSN (print): 0361-8609

ISSN (electronic): 1096-8652

Publisher: John Wiley & Sons, Inc.


DOI: 10.1002/ajh.10365

PubMed id: 12879429


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