Simultaneous detection of ABL1 mutation and IKZF1 deletion in Philadelphia chromosome-positive acute lymphoblastic leukemia using a customized target enrichment system panel

M. Aoe, H. Ishida, T. Matsubara, S. Karakawa, H. Kawaguchi, K. Fujiwara, K. Kanamitsu, Kana Washio, K. Okada, Misako Shibakura, Akira Shimada

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Introduction: Recent clinical outcomes of pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) vastly improved owing to tyrosine kinase inhibitor (TKI). However, the genetic status would be different in each case with ABL1 gene mutation or copy number variants (CNVs) such as IKZF1 deletion. In particular, the TKI resistant clone with ABL1 kinase mutation remains problematic. The comprehensive assessment of genetic status including mutation, insertion and deletion (indel) and CNVs is necessary. Methods: We evaluated a next-generation sequencing (NGS)-based customized HaloPlex target enrichment system panel to simultaneously detect coding mutations, indel and CNVs. We analysed approximately 160 known genes associated with hematological disorders in 5 pediatric Ph+ALL patients. Results: Mono-allelic IKZF1 deletions were found in 4 patients at diagnosis. Furthermore, the mono-allelic deletions were found in exons of RB1, EBF1, PAX5 and ETV6 genes. Bi-allelic deletions were detected in CDKN2A and CDKN2B genes in 1 patient. ABL1 mutation was also detected in 1 patient at relapse. These results were almost comparable with the results of the multiplex ligation-dependent probe amplification (MLPA) method or Sanger sequence. Conclusion: Next-generation sequencing-based custom HaloPlex target enrichment system panel allows us to detect the coding mutations, indel, and CNVs in pediatric Ph+ALL simultaneously, and its results seem comparable with those of other methods.

Original languageEnglish
JournalInternational Journal of Laboratory Hematology
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Philadelphia Chromosome
Sequence Deletion
INDEL Mutation
Chromosomes
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Pediatrics
Genes
Protein-Tyrosine Kinases
Mutation
p16 Genes
Multiplex Polymerase Chain Reaction
Amplification
Exons
Phosphotransferases
Clone Cells
Recurrence

Keywords

  • ALL
  • BCR-ABL1
  • HaloPlex
  • Multiplex ligation-dependent probe amplification
  • Ph

ASJC Scopus subject areas

  • Hematology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

@article{12e54d5b2f1a4508b3639835e7a638e8,
title = "Simultaneous detection of ABL1 mutation and IKZF1 deletion in Philadelphia chromosome-positive acute lymphoblastic leukemia using a customized target enrichment system panel",
abstract = "Introduction: Recent clinical outcomes of pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) vastly improved owing to tyrosine kinase inhibitor (TKI). However, the genetic status would be different in each case with ABL1 gene mutation or copy number variants (CNVs) such as IKZF1 deletion. In particular, the TKI resistant clone with ABL1 kinase mutation remains problematic. The comprehensive assessment of genetic status including mutation, insertion and deletion (indel) and CNVs is necessary. Methods: We evaluated a next-generation sequencing (NGS)-based customized HaloPlex target enrichment system panel to simultaneously detect coding mutations, indel and CNVs. We analysed approximately 160 known genes associated with hematological disorders in 5 pediatric Ph+ALL patients. Results: Mono-allelic IKZF1 deletions were found in 4 patients at diagnosis. Furthermore, the mono-allelic deletions were found in exons of RB1, EBF1, PAX5 and ETV6 genes. Bi-allelic deletions were detected in CDKN2A and CDKN2B genes in 1 patient. ABL1 mutation was also detected in 1 patient at relapse. These results were almost comparable with the results of the multiplex ligation-dependent probe amplification (MLPA) method or Sanger sequence. Conclusion: Next-generation sequencing-based custom HaloPlex target enrichment system panel allows us to detect the coding mutations, indel, and CNVs in pediatric Ph+ALL simultaneously, and its results seem comparable with those of other methods.",
keywords = "ALL, BCR-ABL1, HaloPlex, Multiplex ligation-dependent probe amplification, Ph",
author = "M. Aoe and H. Ishida and T. Matsubara and S. Karakawa and H. Kawaguchi and K. Fujiwara and K. Kanamitsu and Kana Washio and K. Okada and Misako Shibakura and Akira Shimada",
year = "2018",
month = "1",
day = "1",
doi = "10.1111/ijlh.12805",
language = "English",
journal = "International Journal of Laboratory Hematology",
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TY - JOUR

T1 - Simultaneous detection of ABL1 mutation and IKZF1 deletion in Philadelphia chromosome-positive acute lymphoblastic leukemia using a customized target enrichment system panel

AU - Aoe, M.

AU - Ishida, H.

AU - Matsubara, T.

AU - Karakawa, S.

AU - Kawaguchi, H.

AU - Fujiwara, K.

AU - Kanamitsu, K.

AU - Washio, Kana

AU - Okada, K.

AU - Shibakura, Misako

AU - Shimada, Akira

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Introduction: Recent clinical outcomes of pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) vastly improved owing to tyrosine kinase inhibitor (TKI). However, the genetic status would be different in each case with ABL1 gene mutation or copy number variants (CNVs) such as IKZF1 deletion. In particular, the TKI resistant clone with ABL1 kinase mutation remains problematic. The comprehensive assessment of genetic status including mutation, insertion and deletion (indel) and CNVs is necessary. Methods: We evaluated a next-generation sequencing (NGS)-based customized HaloPlex target enrichment system panel to simultaneously detect coding mutations, indel and CNVs. We analysed approximately 160 known genes associated with hematological disorders in 5 pediatric Ph+ALL patients. Results: Mono-allelic IKZF1 deletions were found in 4 patients at diagnosis. Furthermore, the mono-allelic deletions were found in exons of RB1, EBF1, PAX5 and ETV6 genes. Bi-allelic deletions were detected in CDKN2A and CDKN2B genes in 1 patient. ABL1 mutation was also detected in 1 patient at relapse. These results were almost comparable with the results of the multiplex ligation-dependent probe amplification (MLPA) method or Sanger sequence. Conclusion: Next-generation sequencing-based custom HaloPlex target enrichment system panel allows us to detect the coding mutations, indel, and CNVs in pediatric Ph+ALL simultaneously, and its results seem comparable with those of other methods.

AB - Introduction: Recent clinical outcomes of pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) vastly improved owing to tyrosine kinase inhibitor (TKI). However, the genetic status would be different in each case with ABL1 gene mutation or copy number variants (CNVs) such as IKZF1 deletion. In particular, the TKI resistant clone with ABL1 kinase mutation remains problematic. The comprehensive assessment of genetic status including mutation, insertion and deletion (indel) and CNVs is necessary. Methods: We evaluated a next-generation sequencing (NGS)-based customized HaloPlex target enrichment system panel to simultaneously detect coding mutations, indel and CNVs. We analysed approximately 160 known genes associated with hematological disorders in 5 pediatric Ph+ALL patients. Results: Mono-allelic IKZF1 deletions were found in 4 patients at diagnosis. Furthermore, the mono-allelic deletions were found in exons of RB1, EBF1, PAX5 and ETV6 genes. Bi-allelic deletions were detected in CDKN2A and CDKN2B genes in 1 patient. ABL1 mutation was also detected in 1 patient at relapse. These results were almost comparable with the results of the multiplex ligation-dependent probe amplification (MLPA) method or Sanger sequence. Conclusion: Next-generation sequencing-based custom HaloPlex target enrichment system panel allows us to detect the coding mutations, indel, and CNVs in pediatric Ph+ALL simultaneously, and its results seem comparable with those of other methods.

KW - ALL

KW - BCR-ABL1

KW - HaloPlex

KW - Multiplex ligation-dependent probe amplification

KW - Ph

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U2 - 10.1111/ijlh.12805

DO - 10.1111/ijlh.12805

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JO - International Journal of Laboratory Hematology

JF - International Journal of Laboratory Hematology

SN - 1751-5521

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