title: Whole-exome sequencing reveals potential molecular predictors of relapse after discontinuation of the targeted therapy in chronic myeloid leukemia patients.
abstract: Chronic myeloid leukemia (CML) is a myeloproliferative disease well treated by tyrosine kinase inhibitors (TKIs). The aim was to identify genes with a predictive value for relapse-free survival after TKI cessation in CML patients. We performed whole-exome sequencing of DNA from six CML patients in long-lasting deep molecular remission. Patients were divided into two groups with relapse (n = 3) and without relapse (n = 3) after TKI discontinuation. We found variants in genes CYP1B1, ALPK2, and IRF1 in group of patients with relapse and one variant in gene PARP9 in group of patients without relapse. We verified prognostic value of the found markers in a small group of patients with TKI discontinuation and demonstrated their high sensitivity (77%), specificity (86%), positive (85%), and negative (79%) predictive values. Thus we revealed genetic variants, which are potential markers of outcome prediction in CML patients after TKI discontinuation.
authors.affiliation: a Federal State Budgetary Institution "Research Centre for Medical Genetics" , Moscow , Russian Federation ;
authors.forename: Svetlana A
authors.initials: SA
authors.lastname: Smirnikhina
authors.affiliation: a Federal State Budgetary Institution "Research Centre for Medical Genetics" , Moscow , Russian Federation ;|b The Russian National Research Medical University Named after N.I. Pirogov , Moscow , Russian Federation ;
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Lavrov
authors.affiliation: c Scientific and Advisory Department of Chemotherapy of Myeloproliferative Disorders , Federal State-Funded Institution "National Research Center for Hematology" of the Ministry of Healthcare of the Russian Federation , Moscow , Russian Federation.
authors.forename: Ekaterina Yu
authors.initials: EY
authors.lastname: Chelysheva
authors.affiliation: a Federal State Budgetary Institution "Research Centre for Medical Genetics" , Moscow , Russian Federation ;
authors.forename: Elmira P
authors.initials: EP
authors.lastname: Adilgereeva
authors.affiliation: c Scientific and Advisory Department of Chemotherapy of Myeloproliferative Disorders , Federal State-Funded Institution "National Research Center for Hematology" of the Ministry of Healthcare of the Russian Federation , Moscow , Russian Federation.
authors.forename: Oleg A
authors.initials: OA
authors.lastname: Shukhov
authors.affiliation: c Scientific and Advisory Department of Chemotherapy of Myeloproliferative Disorders , Federal State-Funded Institution "National Research Center for Hematology" of the Ministry of Healthcare of the Russian Federation , Moscow , Russian Federation.
authors.forename: Anna
authors.initials: A
authors.lastname: Turkina
authors.affiliation: a Federal State Budgetary Institution "Research Centre for Medical Genetics" , Moscow , Russian Federation ;|b The Russian National Research Medical University Named after N.I. Pirogov , Moscow , Russian Federation ;
authors.forename: Sergey I
authors.initials: SI
authors.lastname: Kutsev
mesh_terms: D000328:Adult; D000483:Alleles; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D019295:Computational Biology; D005260:Female; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D012008:Recurrence; D000073359:Exome Sequencing
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors
keywords: Chronic myeloid leukemia; TKI discontinuation; exome; molecular predictors; relapse