DNA methylation holds prognostic information in relapsed precursor B-cell acute lymphoblastic leukemia

Clin Epigenetics. 2018 Mar 5:10:31. doi: 10.1186/s13148-018-0466-3. eCollection 2018.

Abstract

Background: Few biological markers are associated with survival after relapse of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In pediatric T-cell ALL, we have identified promoter-associated methylation alterations that correlate with prognosis. Here, the prognostic relevance of CpG island methylation phenotype (CIMP) classification was investigated in pediatric BCP-ALL patients.

Methods: Six hundred and one BCP-ALL samples from Nordic pediatric patients (age 1-18) were CIMP classified at initial diagnosis and analyzed in relation to clinical data.

Results: Among the 137 patients that later relapsed, patients with a CIMP- profile (n = 42) at initial diagnosis had an inferior overall survival (pOS5years 33%) compared to CIMP+ patients (n = 95, pOS5years 65%) (p = 0.001), which remained significant in a Cox proportional hazards model including previously defined risk factors.

Conclusion: CIMP classification is a strong candidate for improved risk stratification of relapsed BCP-ALL.

Keywords: BCP-ALL; CIMP; DNA methylation; Prognosis; Relapse; Risk stratification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • CpG Islands
  • DNA Methylation*
  • Epigenesis, Genetic
  • Female
  • Humans
  • Infant
  • Male
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / classification*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Prognosis
  • Proportional Hazards Models
  • Survival Analysis