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

Vicent Guillem; Paula Amat; Francisco Cervantes; Alberto Alvarez-Larrán; Jose Cervera; Margherita Maffioli; Beatriz Bellosillo; María Collado; Isabel Marugán; Francisco Martínez-Ruiz; Juan-Carlos Hernández-Boluda

doi:10.1016/j.leukres.2011.06.011

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

Leuk Res. 2012 Feb;36(2):174-81. doi: 10.1016/j.leukres.2011.06.011. Epub 2011 Jul 2.

Authors

Vicent Guillem¹, Paula Amat, Francisco Cervantes, Alberto Alvarez-Larrán, Jose Cervera, Margherita Maffioli, Beatriz Bellosillo, María Collado, Isabel Marugán, Francisco Martínez-Ruiz, Juan-Carlos Hernández-Boluda

Affiliation

¹ Department of Hematology and Medical Oncology, Hospital Clínico Universitario, Avd. Blasco Ibáñez 17, 46010 Valencia, Spain.

PMID: 21724255
DOI: 10.1016/j.leukres.2011.06.011

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.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Antineoplastic Agents / therapeutic use*
Benzamides
Case-Control Studies
DNA / genetics
Female
Genotype
Humans
Imatinib Mesylate
Leukemia, Myeloid, Chronic-Phase / diagnosis
Leukemia, Myeloid, Chronic-Phase / drug therapy*
Leukemia, Myeloid, Chronic-Phase / genetics*
Male
Middle Aged
Piperazines / therapeutic use*
Polymorphism, Single Nucleotide / genetics*
Prognosis
Protein Tyrosine Phosphatase, Non-Receptor Type 22 / genetics*
Pyrimidines / therapeutic use*
Real-Time Polymerase Chain Reaction
Suppressor of Cytokine Signaling 1 Protein
Suppressor of Cytokine Signaling Proteins / genetics*
Young Adult

Substances

Antineoplastic Agents
Benzamides
Piperazines
Pyrimidines
SOCS1 protein, human
Suppressor of Cytokine Signaling 1 Protein
Suppressor of Cytokine Signaling Proteins
Imatinib Mesylate
DNA
PTPN22 protein, human
Protein Tyrosine Phosphatase, Non-Receptor Type 22