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Jul, 2022;113 (7): 2472-2476.

PAX5 alterations in an infant case of KMT2A-rearranged leukemia with lineage switch.

Koji Nakajima, Hirohito Kubota, Itaru Kato, Kiyotaka Isobe, Hiroo Ueno, Kagehiro Kozuki, Kuniaki Tanaka, Naoko Kawabata, Takashi Mikami, Kosuke Tamefusa, Ritsuo Nishiuchi, Satoshi Saida, Katsutsugu Umeda, Hidefumi Hiramatsu, Souichi Adachi, Junko Takita
Author Information
  1. Koji Nakajima: Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  2. Hirohito Kubota: Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan. ORCID
  3. Itaru Kato: Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan. ORCID
  4. Kiyotaka Isobe: Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  5. Hiroo Ueno: Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  6. Kagehiro Kozuki: Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  7. Kuniaki Tanaka: Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  8. Naoko Kawabata: Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  9. Takashi Mikami: Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  10. Kosuke Tamefusa: Department of Pediatrics, Kochi Health Sciences Center, Kochi, Japan. ORCID
  11. Ritsuo Nishiuchi: Department of Pediatrics, Kochi Health Sciences Center, Kochi, Japan.
  12. Satoshi Saida: Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  13. Katsutsugu Umeda: Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan. ORCID
  14. Hidefumi Hiramatsu: Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan. ORCID
  15. Souichi Adachi: Department of Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  16. Junko Takita: Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan. ORCID
PMID: 35467057 DOI: 10.1111/cas.15380

Abstract

Lineage switch is a rare event at leukemic relapse. While mostly known to occur in KMT2A-rearranged infant leukemia, the underlying mechanism is yet to be depicted. This case report describes a female infant who achieved remission of KMT2A-MLLT3-rearranged acute monocytic leukemia, but 6 months thereafter, relapsed as KMT2A-MLLT3-rearranged acute lymphocytic leukemia. Whole exome sequencing of the bone marrow obtained pre-post lineage switch revealed two somatic mutations of PAX5 in the relapse sample. These two PAX5 alterations were suggested to be loss of function, thus to have played the driver role in the lineage switch from acute monocytic leukemia to acute lymphocytic leukemia.

Keywords

KMT2A rearrangement PAX5 infant leukemia lineage switch whole exome sequencing

References

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Grants

  1. /Japan Leukemia Research Fund
  2. JP17H04224/JSPS KAKENHI
  3. JP18K19467/JSPS KAKENHI
  4. JP19J11112/JSPS KAKENHI
  5. JP20H00528/JSPS KAKENHI
  6. JP21K19405/JSPS KAKENHI
  7. JP20cm0106509h9905/Project for Cancer Research and Therapeutic Evolution
  8. JP19ck0106468h0001/Japan Agency for Medical Research and Development
  9. JP21ck0106531/Japan Agency for Medical Research and Development
  10. /The Mother and Child Health Foundation
  11. /Princess Takamatsu Cancer Research Fund

MeSH Term

Bone Marrow
Child
Female
Histone-Lysine N-Methyltransferase
Humans
Infant
Leukemia, Monocytic, Acute
Leukemia, Myeloid, Acute
Myeloid-Lymphoid Leukemia Protein
PAX5 Transcription Factor
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Recurrence

Chemicals

KMT2A protein, human
PAX5 Transcription Factor
PAX5 protein, human
Myeloid-Lymphoid Leukemia Protein
Histone-Lysine N-Methyltransferase
Case Reports Journal Article
Article has an altmetric score of 1

Word Cloud

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