Association between Germline Single-Nucleotide Variants in ADME Genes and Major Molecular Response to Imatinib in Chronic Myeloid Leukemia Patients
Estrada Barreras, Natalia (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Zamora, Lurdes (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Ferrer-Marín, Francisca (Hospital General Universitario Morales Meseguer (Múrcia))
Palomo Sanchís, Laura (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
García, Olga (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Vélez, Patricia (Hospital Duran i Reynals (Barcelona))
De la Fuente, Iris (Hospital Universitari de Girona Doctor Josep Trueta)
Sagüés, Miguel (Hospital Universitari de Girona Doctor Josep Trueta)
Cabezón, Marta (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Cortés, Montserrat (Hospital de Granollers, 08402 Granollers, Spain)
Vallansot, Rolando Omar (Hospital Universitari Joan XXIII de Tarragona)
Senín-Magán, María Alicia (Hospital Duran i Reynals (Barcelona))
Boque, Concepcion (Hospital Duran i Reynals (Barcelona))
Xicoy, Blanca (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Universitat Autònoma de Barcelona

Date:	2022
Abstract:	Imatinib is the most common first-line tyrosine kinase inhibitor (TKI) used to treat chronic-phase chronic myeloid leukemia (CP-CML). However, only a proportion of patients achieve major molecular response (MMR), so there is a need to find biological factors that aid the selection of the optimal therapeutic strategy (imatinib vs. more potent second-generation TKIs). The aim of this retrospective study was to understand the contribution of germline single-nucleotide variants (gSNVs) in the achievement of MMR with imatinib. In particular, a discovery cohort including 45 CP-CML patients was analyzed through the DMET array, which interrogates 1936 variants in 231 genes related to the absorption, distribution, metabolism and excretion (ADME) process. Variants statistically significant in the discovery cohort were then tested in an extended and independent cohort of 137 CP-CML patients. Finally, a total of 7 gSNVs (ABCG1 -rs492338, ABCB11 -rs496550, ABCB11 -rs497692, CYP2D6 -rs1135840, CYP11B1 -rs7003319, MAT1A -rs4934027 and SLC22A1 -rs628031) and one haplotype in the ABCB11 gene were significantly associated with the achievement of MMR with first-line imatinibtreatment. In conclusion, we identified a genetic signature of response to imatinib in CP-CML patients that could be useful in selecting those patients that may benefit from starting imatinib as first-line therapy, therefore avoiding the toxicity related to second-generation TKIs.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Chronic myeloid leukemia ; Imatinib ; Major molecular response ; Single-nucleotide polymorphisms
Published in:	Journal of clinical medicine, Vol. 11 (october 2022) , ISSN 2077-0383

DOI: 10.3390/jcm11206217
PMID: 36294538

15 p, 1.4 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
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