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RESEARCH PRODUCT

Functional polymorphisms in SOCS1 and PTPN22 genes correlate with the response to imatinib treatment in newly diagnosed chronic-phase chronic myeloid leukemia.

Francisco Martínez-ruizJuan Carlos Hernández-boludaJosé CerveraIsabel MarugánMaria ColladoFrancisco CervantesPaula AmatAlberto Alvarez-larránMargherita MaffioliVicent GuillemBeatriz Bellosillo

subject

OncologyAdultMaleCancer Researchmedicine.medical_specialtyAdolescentGenotypeSingle-nucleotide polymorphismAntineoplastic AgentsSuppressor of Cytokine Signaling ProteinsBiologyReal-Time Polymerase Chain ReactionPolymorphism Single NucleotidePiperazinesPTPN22Young AdultSuppressor of Cytokine Signaling 1 Proteinhemic and lymphatic diseasesInternal medicineGenotypemedicineSNPHumansAlleleAgedSuppressor of cytokine signaling 1ImatinibProtein Tyrosine Phosphatase Non-Receptor Type 22HematologyDNAMiddle AgedPrognosisPyrimidinesOncologyCase-Control StudiesImmunologyBenzamidesLeukemia Myeloid Chronic-PhaseImatinib MesylateFemaleSokal Scoremedicine.drug

description

a b s t r a c t The function of the natural modulators of BCR-ABL-induced signaling pathways could influence the results to imatinib treatment. We assessed the association between single nucleotide polymorphisms (SNPs) on genes of the phosphatase family and the suppressors of cytokine signaling and the response to imatinib in 105 patients newly diagnosed with chronic-phase CML. SNPs in SOCS1 (rs243327) and PTPN22 (rs2476601) genes correlated with the risk of primary resistance to imatinib. A high-risk Sokal score, the T allele in PTPN22 SNP, and each copy of the C allele in SOCS1 SNP were adverse prognostic factors for failure-free survival (FFS). Based on such parameters, three risk groups were identified, with the 5-year FFS for each group being 95%, 75%, and 50%, respectively (P < 0.001). A simple predictive model including Sokal score and genotype of SOCS1 and PTPN22 SNPs may be useful in the selection of the initial treatment in CML.

yearjournalcountryeditionlanguage
2011-05-10Leukemia research
10.1016/j.leukres.2011.06.011https://pubmed.ncbi.nlm.nih.gov/21724255