HLA CW3 and HLA CW4 have a protective effect on acquisition of chronic myeloid leukemia on Mexican patients.

INTRODUCTION

Chronic myeloid leukemia (CML) is characterized by a chromosomal translocation t(9; 22) resulting in the chimeric ber-abl oncogene that encode for the p210 protein which has an increased tyrosine kinase activity. The fusion part of this protein contains a novel aminoacid sequence. If peptides derived from this leukemia-specific part of p210 are expressed in the context of HLA molecules on malignant cells this may elicit immunologically specific responses. Recent studies using synthetic peptides identical to the bcr-abl fusion region revealed that breakpoint specific peptides are capable of binding to the class I molecules HLA-A3, -A11 and -B8. It has been shown that individuals expressing HLA-A3 or HLA-B8 have a diminished risk for development of CML in Caucasoid populations. Other authors have reported a statistically significant increase in the frequency of Cw3 and Cw4 antigens in Causcasoids and European CML patients. These data suggested that Cw3 and Cw4 may be markers for CML susceptibility on these populations.

OBJECTIVE

To asses a possible susceptibility effect of these HLA molecules we studied 63 CML Mexican Mestizo patients and 746 healthy subjects for the distribution of HLA class I and class II molecules.

RESULTS

The gene products that showed statistically significant differences between CML patients and controls were DR14, DR3, Cw3 and Cw4. DR14 and DR3 were significantly increased in the patients group with respect to the controls group (DR14 antigen frequency: 3.17% vs. 0.29%; p = 0.03; DR3 20.63% vs. 8.33%; p = 0.0001). Cw3 and Cw4 were significantly decreased in the patient group (Cw3 26.9% vs. 49.11%; p = 0.03; Cw4 antigen frequency 23.8% vs. 86.28%; p = 0.0000001). The relative risk for DR14 was 10.48 (95% CI 1.52-79.29) and for DR3 was 3.96 (95% CI 2.05-7.71). The relative risk for Cw3 was 0.38 (95% CI 0.08-1.79) and for Cw4 was 0.11 (95% CI 0.048-0.81).

CONCLUSION

These results suggest that the development of CML is apparently associated with HLA phenotypes specific to each population, and indicate that Cw3 and Cw4 expression may result in a protective effect on the CML acquisition on Mexican Mestizo population probably by bcr-abl breakpoint peptides presentation through these HLA molecules.