DNA methylation holds prognostic information in relapsed precursor B-cell acute lymphoblastic leukemia
AuthorBorssén, Magnus; Nordlund, Jessica; Haider, Zahra; Landfors, Mattias; Larsson, Pär; Kanerva, Jukka; Schmiegelow, Kjeld; Flægstad, Trond; Jónsson, Ólafur Gísli; Frost, Britt-Marie; Palle, Josefine; Forestier, Erik; Heyman, Mats; Hultdin, Magnus; Lönnerholm, Gudmar; Degerman, Sofie
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.