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

Landspitali - The National University Hospital of Iceland

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Journal	Clinical Epigenetics
DOIs	https://doi.org/10.1186/s13148-018-0466-3
Publication status	Published - 5 Mar 2018

Other keywords

Hvítblæði
Börn
Sjúkdómshorfur
PED12
DNA Methylation
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Prognosis
Child
Minors

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10.1186/s13148-018-0466-3

https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-018-0466-3

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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. https://doi.org/10.1186/s13148-018-0466-3

@article{dcec5233a0964b6ba52fcb1643d1f624,

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 = "Hv{\'i}tbl{\ae}{\dh}i, B{\"o}rn, Sj{\'u}kd{\'o}mshorfur, PED12, DNA Methylation, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Prognosis, Child, Minors, Hv{\'i}tbl{\ae}{\dh}i, B{\"o}rn, Sj{\'u}kd{\'o}mshorfur, PED12, DNA Methylation, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Prognosis, Child, Minors",

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 Britt-Marie Frost and Josefine Palle and Erik Forestier and Mats Heyman and Magnus Hultdin and Gudmar L{\"o}nnerholm and Sofie Degerman",

year = "2018",

month = mar,

day = "5",

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

language = "English",

journal = "Clinical Epigenetics",

issn = "1868-7075",

publisher = "BioMed Central Ltd.",

}

Borssén, M, Nordlund, J, Haider, Z, Landfors, M, Larsson, P, Kanerva, J, Schmiegelow, K, Flaegstad, T, Jónsson, ÓG, 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. https://doi.org/10.1186/s13148-018-0466-3

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 - 2018/3/5

Y1 - 2018/3/5

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 - Hvítblæði

KW - Börn

KW - Sjúkdómshorfur

KW - PED12

KW - DNA Methylation

KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma

KW - Prognosis

KW - Child

KW - Minors

KW - Hvítblæði

KW - Börn

KW - Sjúkdómshorfur

KW - PED12

KW - DNA Methylation

KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma

KW - Prognosis

KW - Child

KW - Minors

U2 - 10.1186/s13148-018-0466-3

DO - 10.1186/s13148-018-0466-3

M3 - Article

JO - Clinical Epigenetics

JF - Clinical Epigenetics

SN - 1868-7075

ER -

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

Abstract

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