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

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.

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.

Among the 137 patients that later relapsed, patients with a CIMP- profile (n = 42) at initial diagnosis had an inferior overall survival (pOS_5years 33%) compared to CIMP+ patients (n = 95, pOS_5years 65%) (p = 0.001), which remained significant in a Cox proportional hazards model including previously defined risk factors.

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