ZNF384-related fusion genes define a subgroup of childhood B-cell precursor acute lymphoblastic leukemia with a characteristic immunotype

Grupo Español de Neoplasias Mieloproliferativas Filadelfia Negativas

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Fusion genes involving ZNF384 have recently been identified in Bcell precursor acute lymphoblastic leukemia, and 7 fusion partners have been reported. We further characterized this type of fusion gene by whole transcriptome sequencing and/or polymerase chain reaction. In addition to previously reported genes, we identified BMP2K as a novel fusion partner for ZNF384. Including the EP300-ZNF384 that we reported recently, the total frequency of ZNF384-related fusion genes was 4.1% in 291 B-cell precursor acute lymphoblastic leukemia patients enrolled in a single clinical trial, and TCF3-ZNF384 was the most recurrent, with a frequency of 2.4%. The characteristic immunophenotype of weak CD10 and aberrant CD13 and/or CD33 expression was revealed to be a common feature of the leukemic cells harboring ZNF384-related fusion genes. The signature gene expression profile in TCF3-ZNF384-positive patients was enriched in hematopoietic stem cell features and related to that of EP300-ZNF384-positive patients, but was significantly distinct from that of TCF3-PBX1-positive and ZNF384-fusion-negative patients. However, clinical features of TCF3- ZNF384-positive patients are markedly different from those of EP300-ZNF384-positive patients, exhibiting higher cell counts and a younger age at presentation. TCF3-ZNF384-positive patients revealed a significantly poorer steroid response and a higher frequency of relapse, and the additional activating mutations in RAS signaling pathway genes were detected by whole exome analysis in some of the cases. Our observations indicate that ZNF384-related fusion genes consist of a distinct subgroup of B-cell precursor acute lymphoblastic leukemia with a characteristic immunophenotype, while the clinical features depend on the functional properties of individual fusion partners.

Original languageEnglish
Pages (from-to)118-129
Number of pages12
JournalHaematologica
Volume102
Issue number1
DOIs
Publication statusPublished - 01-01-2017

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B-Lymphoid Precursor Cells
Gene Fusion
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Transcriptome
Exome
Hematopoietic Stem Cells
Genes
Cell Count
Steroids
Clinical Trials
Recurrence
Polymerase Chain Reaction
Mutation

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Grupo Español de Neoplasias Mieloproliferativas Filadelfia Negativas. / ZNF384-related fusion genes define a subgroup of childhood B-cell precursor acute lymphoblastic leukemia with a characteristic immunotype. In: Haematologica. 2017 ; Vol. 102, No. 1. pp. 118-129.
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abstract = "Fusion genes involving ZNF384 have recently been identified in Bcell precursor acute lymphoblastic leukemia, and 7 fusion partners have been reported. We further characterized this type of fusion gene by whole transcriptome sequencing and/or polymerase chain reaction. In addition to previously reported genes, we identified BMP2K as a novel fusion partner for ZNF384. Including the EP300-ZNF384 that we reported recently, the total frequency of ZNF384-related fusion genes was 4.1{\%} in 291 B-cell precursor acute lymphoblastic leukemia patients enrolled in a single clinical trial, and TCF3-ZNF384 was the most recurrent, with a frequency of 2.4{\%}. The characteristic immunophenotype of weak CD10 and aberrant CD13 and/or CD33 expression was revealed to be a common feature of the leukemic cells harboring ZNF384-related fusion genes. The signature gene expression profile in TCF3-ZNF384-positive patients was enriched in hematopoietic stem cell features and related to that of EP300-ZNF384-positive patients, but was significantly distinct from that of TCF3-PBX1-positive and ZNF384-fusion-negative patients. However, clinical features of TCF3- ZNF384-positive patients are markedly different from those of EP300-ZNF384-positive patients, exhibiting higher cell counts and a younger age at presentation. TCF3-ZNF384-positive patients revealed a significantly poorer steroid response and a higher frequency of relapse, and the additional activating mutations in RAS signaling pathway genes were detected by whole exome analysis in some of the cases. Our observations indicate that ZNF384-related fusion genes consist of a distinct subgroup of B-cell precursor acute lymphoblastic leukemia with a characteristic immunophenotype, while the clinical features depend on the functional properties of individual fusion partners.",
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ZNF384-related fusion genes define a subgroup of childhood B-cell precursor acute lymphoblastic leukemia with a characteristic immunotype. / Grupo Español de Neoplasias Mieloproliferativas Filadelfia Negativas.

In: Haematologica, Vol. 102, No. 1, 01.01.2017, p. 118-129.

Research output: Contribution to journalArticle

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T1 - ZNF384-related fusion genes define a subgroup of childhood B-cell precursor acute lymphoblastic leukemia with a characteristic immunotype

AU - Grupo Español de Neoplasias Mieloproliferativas Filadelfia Negativas

AU - Hirabayashi, Shinsuke

AU - Ohki, Kentaro

AU - Nakabayashi, Kazuhiko

AU - Ichikawa, Hitoshi

AU - Momozawa, Yukihide

AU - Okamura, Kohji

AU - Yaguchi, Akinori

AU - Terada, Kazuki

AU - Saito, Yuya

AU - Yoshimi, Ai

AU - Ogata-Kawata, Hiroko

AU - Sakamoto, Hiromi

AU - Kato, Motohiro

AU - Fujimura, Junya

AU - Hino, Moeko

AU - Kinoshita, Akitoshi

AU - Kakuda, Harumi

AU - Kurosawa, Hidemitsu

AU - Kato, Keisuke

AU - Kajiwara, Ryosuke

AU - Moriwaki, Koichi

AU - Morimoto, Tsuyoshi

AU - Nakamura, Kozue

AU - Noguchi, Yasushi

AU - Osumi, Tomoo

AU - Sakashita, Kazuo

AU - Takita, Junko

AU - Yuza, Yuki

AU - Matsuda, Koich

AU - Yoshida, Teruhiko

AU - Matsumoto, Kenji

AU - Hata, Kenichiro

AU - Kubo, Michiaki

AU - Matsubara, Yoichi

AU - Fukushima, Takashi

AU - Koh, Katsuyoshi

AU - Manabe, Atsushi

AU - Ohara, Akira

AU - Kubo, Michiaki

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Y1 - 2017/1/1

N2 - Fusion genes involving ZNF384 have recently been identified in Bcell precursor acute lymphoblastic leukemia, and 7 fusion partners have been reported. We further characterized this type of fusion gene by whole transcriptome sequencing and/or polymerase chain reaction. In addition to previously reported genes, we identified BMP2K as a novel fusion partner for ZNF384. Including the EP300-ZNF384 that we reported recently, the total frequency of ZNF384-related fusion genes was 4.1% in 291 B-cell precursor acute lymphoblastic leukemia patients enrolled in a single clinical trial, and TCF3-ZNF384 was the most recurrent, with a frequency of 2.4%. The characteristic immunophenotype of weak CD10 and aberrant CD13 and/or CD33 expression was revealed to be a common feature of the leukemic cells harboring ZNF384-related fusion genes. The signature gene expression profile in TCF3-ZNF384-positive patients was enriched in hematopoietic stem cell features and related to that of EP300-ZNF384-positive patients, but was significantly distinct from that of TCF3-PBX1-positive and ZNF384-fusion-negative patients. However, clinical features of TCF3- ZNF384-positive patients are markedly different from those of EP300-ZNF384-positive patients, exhibiting higher cell counts and a younger age at presentation. TCF3-ZNF384-positive patients revealed a significantly poorer steroid response and a higher frequency of relapse, and the additional activating mutations in RAS signaling pathway genes were detected by whole exome analysis in some of the cases. Our observations indicate that ZNF384-related fusion genes consist of a distinct subgroup of B-cell precursor acute lymphoblastic leukemia with a characteristic immunophenotype, while the clinical features depend on the functional properties of individual fusion partners.

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