Association of HLA Class I and Class II genes with bcr-abl transcripts in leukemia patients with t(9;22) (q34;q11)

BMC Cancer. 2004 Jun 17:4:25. doi: 10.1186/1471-2407-4-25.

Abstract

Background: Based on the site of breakpoint in t(9;22) (q34;q11), bcr-abl fusion in leukemia patients is associated with different types of transcript proteins. In this study we have seen the association of HLA genes with different types of bcr-abl transcripts. The association could predict the bcr-abl peptide presentation by particular HLA molecules.

Methods: The study included a total of 189 patients of mixed ethnicity with chronic myelogenous leukemia and acute lymphocytic leukemia who were being considered for bone marrow transplantation. Typing of bcr-abl transcripts was done by reverse transcriptase PCR method. HLA typing was performed by molecular methods. The bcr-abl and HLA association was studied by calculating the relative risks and chi-square test.

Results: Significant negative associations (p < 0.05) were observed with HLA-A*02 (b2a2, e1a2), -A*68 (b2a2, b3a2, e1a2), -B*14 (b2a2, b3a2, e1a2), -B*15 (b2a2, b3a2), -B*40 (b2a2), -DQB1*0303 (b2a2, b3a2), -DQB1*0603 (b2a2), -DRB1*0401 (e1a2), -DRB1*0701 (b3a2), and -DRB1*1101 (b2a2).

Conclusions: The negative associations of a particular bcr-abl transcript with specific HLA alleles suggests that these alleles play a critical role in presenting peptides derived from the chimeric proteins and eliciting a successful T-cell cytotoxic response. Knowledge of differential associations between HLA phenotypes and bcr-abl fusion transcript types would help in developing better strategies for immunization with the bcr-abl peptides against t(9;22) (q34;q11)-positive leukemia.

MeSH terms

  • Alleles
  • Chromosomes, Human, Pair 22
  • Chromosomes, Human, Pair 9
  • Fusion Proteins, bcr-abl / blood
  • Fusion Proteins, bcr-abl / genetics*
  • Genes, MHC Class I*
  • Genes, MHC Class II*
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / blood
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / blood
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Translocation, Genetic / genetics*

Substances

  • Fusion Proteins, bcr-abl