title: Functional polymorphisms in SOCS1 and PTPN22 genes correlate with the response to imatinib treatment in newly diagnosed chronic-phase chronic myeloid leukemia.
abstract: 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.
authors: Department of Hematology and Medical Oncology, Hospital Clínico Universitario, Avd. Blasco Ibáñez 17, 46010 Valencia, Spain.
authors: Vicent
authors: V
authors: Guillem
authors: Paula
authors: P
authors: Amat
authors: Francisco
authors: F
authors: Cervantes
authors: Alberto
authors: A
authors: Alvarez-Larrán
authors: Jose
authors: J
authors: Cervera
authors: Margherita
authors: M
authors: Maffioli
authors: Beatriz
authors: B
authors: Bellosillo
authors: María
authors: M
authors: Collado
authors: Isabel
authors: I
authors: Marugán
authors: Francisco
authors: F
authors: Martínez-Ruiz
authors: Juan-Carlos
authors: JC
authors: Hernández-Boluda
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D000068877:Imatinib Mesylate; D015466:Leukemia, Myeloid, Chronic-Phase / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D011743:Pyrimidines / Q000627:therapeutic use*; D060888:Real-Time Polymerase Chain Reaction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D000068877:Imatinib Mesylate; D004247:DNA; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22