Premium
XPC genetic polymorphisms correlate with the response to imatinib treatment in patients with chronic phase chronic myeloid leukemia
Author(s) -
Guillem Vicent M.,
Cervantes Francisco,
Martínez Jesús,
AlvarezLarrán Alberto,
Collado María,
Camós Mireia,
Sureda Anna,
Maffioli Margherita,
Marugán Isabel,
HernándezBoluda JuanCarlos
Publication year - 2010
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.21726
Subject(s) - imatinib , myeloid leukemia , haplotype , single nucleotide polymorphism , odds ratio , oncology , cancer research , biology , medicine , immunology , genetics , genotype , gene
Chronic myeloid leukemia (CML) is driven by the BCR‐ABL protein, which promotes the proliferation and viability of the leukemic cells. Moreover, BCR‐ABL induces genomic instability that can contribute to the emergence of resistant clones to the ABL kinase inhibitors. It is currently unknown whether the inherited individual capability to repair DNA damage could affect the treatment results. To address this, a comprehensive analysis of single nucleotide polimorfisms (SNPs) on the nucleotide excision repair (NER) genes ( ERCC2‐ERCC8 , RPA1‐RPA3 , LIG1 , RAD23B , XPA , XPC ) was performed in 92 chronic phase CML patients treated with imatinib upfront. ERCC5 and XPC SNPs correlated with the response to imatinib. Haplotype analysis of XPC showed that the wild‐type haplotype (499C‐939A) was associated with a better response to imatinib. Moreover, the 5‐year failure free survival for CA carriers was significantly better than that of the non‐CA carriers (98% vs. 73%; P = 0.02). In the multivariate logistic model with genetic data and clinical covariates, the hemoglobin (Hb) level and the XPC haplotype were independently associated with the treatment response, with patients having a Hb ≤11 g/dl (Odds ratio [OR] = 5.0, 95% confidence interval [CI] = 1.5–16.1) or a non‐CA XPC haplotype (OR = 4.1, 95% CI = 1.6–10.6) being at higher risk of suboptimal response/treatment failure. Our findings suggest that genetic polymorphisms in the NER pathway may influence the results to imatinib treatment in CML. Am. J. Hematol., 2010. © 2010 Wiley‐Liss, Inc.