ADAMTSL5 and CDH11: putative epigenetic markers for therapeutic resistance in acute lymphoblastic leukemia

Maha Abdullah, Chee Wei Choo, Hamidah Alias, Eni Juraidah Abdul Rahman, Hishamshah Mohd Ibrahim, A. Rahman A. Jamal, Noor Hamidah Hussin

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background and objectives: DNA hypermethylation has been linked to poor treatment outcome in childhood acute lymphoblastic leukemia (ALL). Genes differentially methylated in the chemoresponsive pre-B-ALL compared to chemoresistant pre-B-ALL cases provide potential prognostic markers. Methods: DNA methylation profiles of five B-ALL childhood patients who achieved morphological complete remission (chemoresponsive) and five B-ALL patients who did not (chemoresistant) after induction treatments as well as four normal controls were compared on 27 000 CpG sites microarray chips. Subsequently, methylation-specific polymerase chain reaction (MSP) on selected hypermethylated genes was conducted on an additional 37 chemoresponsive and 9 chemoresistant B-ALL samples and 2 normal controls. Results: Both methods were found to be highly correlated. Unsupervised principal component analysis showed that the chemotherapy-responsive and -resistant B-ALL patients could be segregated from one another. Selection of segregated genes at high stringency identified two potential genes (CDH11 and ADAMTSL5). MSP analysis on the larger cohort of samples (42 chemoresponsive, 14 chemoresistant B-ALL samples and 6 normal controls) revealed significantly higher rates of hypermethylation in chemoresistant samples for ADAMTSL5 (93 vs. 38%; p = 0.0001) and CDH11 (79% vs. 40%, p < 0.01). All control cases remained unmethylated. Conclusion: Chemoresistant B-ALL patients are associated with increased methylation in ADAMTSL5 and CDH11. These findings need to be validated in a larger group of patients, and the functional biological and prognostic significance of differential methylation needs to be studied further.

Original languageEnglish
Pages (from-to)1-6
Number of pages6
JournalHematology
DOIs
Publication statusAccepted/In press - 16 Mar 2017

Fingerprint

Precursor Cell Lymphoblastic Leukemia-Lymphoma
Epigenomics
Methylation
Therapeutics
Genes
DNA Methylation
Principal Component Analysis
Drug Therapy
Polymerase Chain Reaction
DNA

Keywords

  • Acute lymphoblastic leukemia (ALL)
  • epigenetic marker
  • methylation

ASJC Scopus subject areas

  • Medicine(all)
  • Hematology

Cite this

ADAMTSL5 and CDH11 : putative epigenetic markers for therapeutic resistance in acute lymphoblastic leukemia. / Abdullah, Maha; Choo, Chee Wei; Alias, Hamidah; Abdul Rahman, Eni Juraidah; Ibrahim, Hishamshah Mohd; A. Jamal, A. Rahman; Hussin, Noor Hamidah.

In: Hematology, 16.03.2017, p. 1-6.

Research output: Contribution to journalArticle

@article{78fc6c3536f346c180c9f5f2b9c0fd91,
title = "ADAMTSL5 and CDH11: putative epigenetic markers for therapeutic resistance in acute lymphoblastic leukemia",
abstract = "Background and objectives: DNA hypermethylation has been linked to poor treatment outcome in childhood acute lymphoblastic leukemia (ALL). Genes differentially methylated in the chemoresponsive pre-B-ALL compared to chemoresistant pre-B-ALL cases provide potential prognostic markers. Methods: DNA methylation profiles of five B-ALL childhood patients who achieved morphological complete remission (chemoresponsive) and five B-ALL patients who did not (chemoresistant) after induction treatments as well as four normal controls were compared on 27 000 CpG sites microarray chips. Subsequently, methylation-specific polymerase chain reaction (MSP) on selected hypermethylated genes was conducted on an additional 37 chemoresponsive and 9 chemoresistant B-ALL samples and 2 normal controls. Results: Both methods were found to be highly correlated. Unsupervised principal component analysis showed that the chemotherapy-responsive and -resistant B-ALL patients could be segregated from one another. Selection of segregated genes at high stringency identified two potential genes (CDH11 and ADAMTSL5). MSP analysis on the larger cohort of samples (42 chemoresponsive, 14 chemoresistant B-ALL samples and 6 normal controls) revealed significantly higher rates of hypermethylation in chemoresistant samples for ADAMTSL5 (93 vs. 38{\%}; p = 0.0001) and CDH11 (79{\%} vs. 40{\%}, p < 0.01). All control cases remained unmethylated. Conclusion: Chemoresistant B-ALL patients are associated with increased methylation in ADAMTSL5 and CDH11. These findings need to be validated in a larger group of patients, and the functional biological and prognostic significance of differential methylation needs to be studied further.",
keywords = "Acute lymphoblastic leukemia (ALL), epigenetic marker, methylation",
author = "Maha Abdullah and Choo, {Chee Wei} and Hamidah Alias and {Abdul Rahman}, {Eni Juraidah} and Ibrahim, {Hishamshah Mohd} and {A. Jamal}, {A. Rahman} and Hussin, {Noor Hamidah}",
year = "2017",
month = "3",
day = "16",
doi = "10.1080/10245332.2017.1299417",
language = "English",
pages = "1--6",
journal = "Hematology",
issn = "1024-5332",
publisher = "Taylor and Francis Ltd.",

}

TY - JOUR

T1 - ADAMTSL5 and CDH11

T2 - putative epigenetic markers for therapeutic resistance in acute lymphoblastic leukemia

AU - Abdullah, Maha

AU - Choo, Chee Wei

AU - Alias, Hamidah

AU - Abdul Rahman, Eni Juraidah

AU - Ibrahim, Hishamshah Mohd

AU - A. Jamal, A. Rahman

AU - Hussin, Noor Hamidah

PY - 2017/3/16

Y1 - 2017/3/16

N2 - Background and objectives: DNA hypermethylation has been linked to poor treatment outcome in childhood acute lymphoblastic leukemia (ALL). Genes differentially methylated in the chemoresponsive pre-B-ALL compared to chemoresistant pre-B-ALL cases provide potential prognostic markers. Methods: DNA methylation profiles of five B-ALL childhood patients who achieved morphological complete remission (chemoresponsive) and five B-ALL patients who did not (chemoresistant) after induction treatments as well as four normal controls were compared on 27 000 CpG sites microarray chips. Subsequently, methylation-specific polymerase chain reaction (MSP) on selected hypermethylated genes was conducted on an additional 37 chemoresponsive and 9 chemoresistant B-ALL samples and 2 normal controls. Results: Both methods were found to be highly correlated. Unsupervised principal component analysis showed that the chemotherapy-responsive and -resistant B-ALL patients could be segregated from one another. Selection of segregated genes at high stringency identified two potential genes (CDH11 and ADAMTSL5). MSP analysis on the larger cohort of samples (42 chemoresponsive, 14 chemoresistant B-ALL samples and 6 normal controls) revealed significantly higher rates of hypermethylation in chemoresistant samples for ADAMTSL5 (93 vs. 38%; p = 0.0001) and CDH11 (79% vs. 40%, p < 0.01). All control cases remained unmethylated. Conclusion: Chemoresistant B-ALL patients are associated with increased methylation in ADAMTSL5 and CDH11. These findings need to be validated in a larger group of patients, and the functional biological and prognostic significance of differential methylation needs to be studied further.

AB - Background and objectives: DNA hypermethylation has been linked to poor treatment outcome in childhood acute lymphoblastic leukemia (ALL). Genes differentially methylated in the chemoresponsive pre-B-ALL compared to chemoresistant pre-B-ALL cases provide potential prognostic markers. Methods: DNA methylation profiles of five B-ALL childhood patients who achieved morphological complete remission (chemoresponsive) and five B-ALL patients who did not (chemoresistant) after induction treatments as well as four normal controls were compared on 27 000 CpG sites microarray chips. Subsequently, methylation-specific polymerase chain reaction (MSP) on selected hypermethylated genes was conducted on an additional 37 chemoresponsive and 9 chemoresistant B-ALL samples and 2 normal controls. Results: Both methods were found to be highly correlated. Unsupervised principal component analysis showed that the chemotherapy-responsive and -resistant B-ALL patients could be segregated from one another. Selection of segregated genes at high stringency identified two potential genes (CDH11 and ADAMTSL5). MSP analysis on the larger cohort of samples (42 chemoresponsive, 14 chemoresistant B-ALL samples and 6 normal controls) revealed significantly higher rates of hypermethylation in chemoresistant samples for ADAMTSL5 (93 vs. 38%; p = 0.0001) and CDH11 (79% vs. 40%, p < 0.01). All control cases remained unmethylated. Conclusion: Chemoresistant B-ALL patients are associated with increased methylation in ADAMTSL5 and CDH11. These findings need to be validated in a larger group of patients, and the functional biological and prognostic significance of differential methylation needs to be studied further.

KW - Acute lymphoblastic leukemia (ALL)

KW - epigenetic marker

KW - methylation

UR - http://www.scopus.com/inward/record.url?scp=85015187835&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85015187835&partnerID=8YFLogxK

U2 - 10.1080/10245332.2017.1299417

DO - 10.1080/10245332.2017.1299417

M3 - Article

C2 - 28292214

AN - SCOPUS:85015187835

SP - 1

EP - 6

JO - Hematology

JF - Hematology

SN - 1024-5332

ER -