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

Magnus Borssén; Jessica Nordlund; Zahra Haider; Mattias Landfors; Pär Larsson; Jukka Kanerva; Kjeld Schmiegelow; Trond Flaegstad; Ólafur Gísli Jónsson; Britt Marie Frost; Josefine Palle; Erik Forestier; Mats Heyman; Magnus Hultdin; Gudmar Lönnerholm; Sofie Degerman

doi:10.1186/s13148-018-0466-3

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

Magnus Borssén, Jessica Nordlund, Zahra Haider, Mattias Landfors, Pär Larsson, Jukka Kanerva, Kjeld Schmiegelow, Trond Flaegstad, Ólafur Gísli Jónsson, Britt Marie Frost, Josefine Palle, Erik Forestier, Mats Heyman, Magnus Hultdin, Gudmar Lönnerholm, Sofie Degerman^*

^*Corresponding author for this work

Department of Clinical Medicine

8 Citations (Scopus)

49 Downloads (Pure)

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

Original language	English
Article number	31
Journal	Clinical Epigenetics
Volume	10
Number of pages	7
ISSN	1868-7075
DOIs	https://doi.org/10.1186/s13148-018-0466-3
Publication status	Published - 2018

Keywords

BCP-ALL
CIMP
DNA methylation
Prognosis
Relapse
Risk stratification

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Borssén, M., Nordlund, J., Haider, Z., Landfors, M., Larsson, P., Kanerva, J., Schmiegelow, K., Flaegstad, T., Jónsson, Ó. G., Frost, B. M., Palle, J., Forestier, E., Heyman, M., Hultdin, M., Lönnerholm, G., & Degerman, S. (2018). DNA methylation holds prognostic information in relapsed precursor B-cell acute lymphoblastic leukemia. Clinical Epigenetics, 10, [31]. https://doi.org/10.1186/s13148-018-0466-3

Borssén, M, Nordlund, J, Haider, Z, Landfors, M, Larsson, P, Kanerva, J, Schmiegelow, K, Flaegstad, T, Jónsson, ÓG, Frost, BM, Palle, J, Forestier, E, Heyman, M, Hultdin, M, Lönnerholm, G & Degerman, S 2018, 'DNA methylation holds prognostic information in relapsed precursor B-cell acute lymphoblastic leukemia', Clinical Epigenetics, vol. 10, 31. https://doi.org/10.1186/s13148-018-0466-3

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title = "DNA methylation holds prognostic information in relapsed precursor B-cell acute lymphoblastic leukemia",

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",

author = "Magnus Borss{\'e}n and Jessica Nordlund and Zahra Haider and Mattias Landfors and P{\"a}r Larsson and Jukka Kanerva and Kjeld Schmiegelow and Trond Flaegstad and J{\'o}nsson, {{\'O}lafur G{\'i}sli} and Frost, {Britt Marie} and Josefine Palle and Erik Forestier and Mats Heyman and Magnus Hultdin and Gudmar L{\"o}nnerholm and Sofie Degerman",

year = "2018",

doi = "10.1186/s13148-018-0466-3",

language = "English",

volume = "10",

journal = "Clinical Epigenetics (Print)",

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TY - JOUR

T1 - DNA methylation holds prognostic information in relapsed precursor B-cell acute lymphoblastic leukemia

AU - Borssén, Magnus

AU - Nordlund, Jessica

AU - Haider, Zahra

AU - Landfors, Mattias

AU - Larsson, Pär

AU - Kanerva, Jukka

AU - Schmiegelow, Kjeld

AU - Flaegstad, Trond

AU - Jónsson, Ólafur Gísli

AU - Frost, Britt Marie

AU - Palle, Josefine

AU - Forestier, Erik

AU - Heyman, Mats

AU - Hultdin, Magnus

AU - Lönnerholm, Gudmar

AU - Degerman, Sofie

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - BCP-ALL

KW - CIMP

KW - DNA methylation

KW - Prognosis

KW - Relapse

KW - Risk stratification

U2 - 10.1186/s13148-018-0466-3

DO - 10.1186/s13148-018-0466-3

M3 - Journal article

C2 - 29515676

AN - SCOPUS:85043307665

SN - 1868-7075

VL - 10

JO - Clinical Epigenetics (Print)

JF - Clinical Epigenetics (Print)

M1 - 31

ER -

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

Abstract

Keywords

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