Whole-exome sequencing reveals potential molecular predictors of relapse after discontinuation of the targeted therapy in chronic myeloid leukemia patients

Leuk Lymphoma. 2016 Jul;57(7):1669-76. doi: 10.3109/10428194.2015.1132420. Epub 2016 Jan 12.

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.

Keywords: Chronic myeloid leukemia; TKI discontinuation; exome; molecular predictors; relapse.

MeSH terms

  • Adult
  • Alleles
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor*
  • Computational Biology
  • Exome Sequencing*
  • Female
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology*
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Mutation
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use
  • Recurrence

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Protein Kinase Inhibitors