Mundhada Shailendra, Luthra Rajyalakshmi, Cano Pedro
Department of Laboratory Medicine, The University of Texas, M D Anderson Cancer Center, Houston, TX 77030.
BMC Cancer. 2004 Jun 17;4:25. doi: 10.1186/1471-2407-4-25.
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.
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.
Significant negative associations (p < 0.05) were observed with HLA-A02 (b2a2, e1a2), -A68 (b2a2, b3a2, e1a2), -B14 (b2a2, b3a2, e1a2), -B15 (b2a2, b3a2), -B40 (b2a2), -DQB10303 (b2a2, b3a2), -DQB10603 (b2a2), -DRB10401 (e1a2), -DRB10701 (b3a2), and -DRB11101 (b2a2).
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.
基于t(9;22)(q34;q11)断点的位置,白血病患者中的bcr-abl融合与不同类型的转录蛋白相关。在本研究中,我们观察了HLA基因与不同类型的bcr-abl转录本之间的关联。这种关联可以预测特定HLA分子对bcr-abl肽的呈递。
该研究共纳入189例患有慢性粒细胞白血病和急性淋巴细胞白血病的不同种族患者,这些患者正考虑进行骨髓移植。通过逆转录酶PCR方法对bcr-abl转录本进行分型。通过分子方法进行HLA分型。通过计算相对风险和卡方检验研究bcr-abl与HLA的关联。
观察到与HLA-A02(b2a2,e1a2)、-A68(b2a2,b3a2,e1a2)、-B14(b2a2,b3a2,e1a2)、-B15(b2a2,b3a2)、-B40(b2a2)、-DQB10303(b2a2,b3a2)、-DQB10603(b2a2)、-DRB10401(e1a2)、-DRB10701(b3a2)和-DRB11101(b2a2)存在显著负相关(p<0.05)。
特定的bcr-abl转录本与特定HLA等位基因的负相关表明,这些等位基因在呈递源自嵌合蛋白的肽并引发成功的T细胞细胞毒性反应中起关键作用。了解HLA表型与bcr-abl融合转录本类型之间的差异关联将有助于制定更好的策略,用bcr-abl肽针对t(9;22)(q34;q11)阳性白血病进行免疫治疗。