Copy number abnormality of acute lymphoblastic leukemia cell lines based on their genetic subtypes

Chihiro Tomoyasu, Toshihiko Imamura, Toshihiro Tomii, Mio Yano, Daisuke Asai, Hiroaki Goto, Akira Shimada, Masashi Sanada, Shotaro Iwamoto, Junko Takita, Masayoshi Minegishi, Takeshi Inukai, Kanji Sugita, Hajime Hosoi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

In this study, we performed genetic analysis of 83 B cell precursor acute lymphoblastic leukemia (B-ALL) cell lines. First, we performed multiplex ligation-dependent probe amplification analysis to identify copy number abnormalities (CNAs) in eight genes associated with B-ALL according to genetic subtype. In Ph+ B-ALL cell lines, the frequencies of IKZF1, CDKN2A/2B, BTG1, and PAX5 deletion were significantly higher than those in Ph B-ALL cell lines. The frequency of CDKN2A/2B deletion in KMT2A rearranged cell lines was significantly lower than that in non-KMT2A rearranged cell lines. These findings suggest that CNAs are correlated with genetic subtype in B-ALL cell lines. In addition, we determined that three B-other ALL cell lines had IKZF1 deletions (YCUB-5, KOPN49, and KOPN75); we therefore performed comprehensive genetic analysis of these cell lines. YCUB-5, KOPN49, and KOPN75 had P2RY8-CRLF2, IgH-CRLF2, and PAX5-ETV6 fusions, respectively. Moreover, targeted capture sequencing revealed that YCUB-5 had JAK2 R683I and KRAS G12D, and KOPN49 had JAK2 R683G and KRAS G13D mutations. These data may contribute to progress in the field of leukemia research.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalInternational Journal of Hematology
DOIs
Publication statusAccepted/In press - May 21 2018

Fingerprint

Precursor Cell Lymphoblastic Leukemia-Lymphoma
B-Lymphoid Precursor Cells
Cell Line
Multiplex Polymerase Chain Reaction
Leukemia
Mutation
Research
Genes

Keywords

  • Acute lymphoblastic leukemia cell line
  • BTG1
  • CDKN2A
  • CDKN2B
  • Copy number abnormality
  • IKZF1

ASJC Scopus subject areas

  • Hematology

Cite this

Copy number abnormality of acute lymphoblastic leukemia cell lines based on their genetic subtypes. / Tomoyasu, Chihiro; Imamura, Toshihiko; Tomii, Toshihiro; Yano, Mio; Asai, Daisuke; Goto, Hiroaki; Shimada, Akira; Sanada, Masashi; Iwamoto, Shotaro; Takita, Junko; Minegishi, Masayoshi; Inukai, Takeshi; Sugita, Kanji; Hosoi, Hajime.

In: International Journal of Hematology, 21.05.2018, p. 1-7.

Research output: Contribution to journalArticle

Tomoyasu, C, Imamura, T, Tomii, T, Yano, M, Asai, D, Goto, H, Shimada, A, Sanada, M, Iwamoto, S, Takita, J, Minegishi, M, Inukai, T, Sugita, K & Hosoi, H 2018, 'Copy number abnormality of acute lymphoblastic leukemia cell lines based on their genetic subtypes', International Journal of Hematology, pp. 1-7. https://doi.org/10.1007/s12185-018-2474-7
Tomoyasu, Chihiro ; Imamura, Toshihiko ; Tomii, Toshihiro ; Yano, Mio ; Asai, Daisuke ; Goto, Hiroaki ; Shimada, Akira ; Sanada, Masashi ; Iwamoto, Shotaro ; Takita, Junko ; Minegishi, Masayoshi ; Inukai, Takeshi ; Sugita, Kanji ; Hosoi, Hajime. / Copy number abnormality of acute lymphoblastic leukemia cell lines based on their genetic subtypes. In: International Journal of Hematology. 2018 ; pp. 1-7.
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AU - Tomoyasu, Chihiro

AU - Imamura, Toshihiko

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AU - Yano, Mio

AU - Asai, Daisuke

AU - Goto, Hiroaki

AU - Shimada, Akira

AU - Sanada, Masashi

AU - Iwamoto, Shotaro

AU - Takita, Junko

AU - Minegishi, Masayoshi

AU - Inukai, Takeshi

AU - Sugita, Kanji

AU - Hosoi, Hajime

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AB - In this study, we performed genetic analysis of 83 B cell precursor acute lymphoblastic leukemia (B-ALL) cell lines. First, we performed multiplex ligation-dependent probe amplification analysis to identify copy number abnormalities (CNAs) in eight genes associated with B-ALL according to genetic subtype. In Ph+ B-ALL cell lines, the frequencies of IKZF1, CDKN2A/2B, BTG1, and PAX5 deletion were significantly higher than those in Ph− B-ALL cell lines. The frequency of CDKN2A/2B deletion in KMT2A rearranged cell lines was significantly lower than that in non-KMT2A rearranged cell lines. These findings suggest that CNAs are correlated with genetic subtype in B-ALL cell lines. In addition, we determined that three B-other ALL cell lines had IKZF1 deletions (YCUB-5, KOPN49, and KOPN75); we therefore performed comprehensive genetic analysis of these cell lines. YCUB-5, KOPN49, and KOPN75 had P2RY8-CRLF2, IgH-CRLF2, and PAX5-ETV6 fusions, respectively. Moreover, targeted capture sequencing revealed that YCUB-5 had JAK2 R683I and KRAS G12D, and KOPN49 had JAK2 R683G and KRAS G13D mutations. These data may contribute to progress in the field of leukemia research.

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