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 af dette arbejde

Institut for Klinisk Medicin

8 Citationer (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.

Originalsprog	Engelsk
Artikelnummer	31
Tidsskrift	Clinical Epigenetics
Vol/bind	10
Antal sider	7
ISSN	1868-7075
DOI	https://doi.org/10.1186/s13148-018-0466-3
Status	Udgivet - 2018

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10.1186/s13148-018-0466-3Licens: CC BY

s13148-018-0466-3Forlagets udgivne version, 648 KBLicens: CC BY

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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, Artikel 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, bind 10, 31. https://doi.org/10.1186/s13148-018-0466-3

@article{adb01d8d204849b6b1f96b039a470757,

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",

issn = "1868-7075",

publisher = "BioMed Central Ltd.",

}

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

JF - Clinical Epigenetics

M1 - 31

ER -

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

Abstract

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