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

• Published in: Cancer science Vol. 113; no. 7; pp. 2472 - 2476
• Main Authors: Nakajima, Koji, Kubota, Hirohito, Kato, Itaru, Isobe, Kiyotaka, Ueno, Hiroo, Kozuki, Kagehiro, Tanaka, Kuniaki, Kawabata, Naoko, Mikami, Takashi, Tamefusa, Kosuke, Nishiuchi, Ritsuo, Saida, Satoshi, Umeda, Katsutsugu, Hiramatsu, Hidefumi, Adachi, Souichi, Takita, Junko
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.07.2022; John Wiley and Sons Inc
• Subjects: Acute monocytic leukemia; Blood; Bone marrow; Case Report; Chemotherapy; Cloning; Flow cytometry; Gene expression; Genomes; infant leukemia; Infants; KMT2A rearrangement; Leukemia; lineage switch; Lymphatic leukemia; Magnetic resonance imaging; Monocytes; Monocytic leukemia; Mutation; PAX5; Pax5 protein; Pediatrics; Remission; Remission (Medicine); Transplants & implants; whole exome sequencing; infant leukemia; PAX5; lineage switch; KMT2A rearrangement; whole exome sequencing
• ISSN: 1347-9032; 1349-7006; 1349-7006
• DOI: 10.1111/cas.15380

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. Whole exome sequencing was undertaken on an infant case of KMT2A‐rearranged leukemia that underwent lineage switch from acute monocytic leukemia to acute lymphocytic leukemia. Two somatic mutations in PAX5 consistent with biallelic targeting were identified in the relapse sample, thus suggesting that the subsequent loss of PAX5 function might have played a driver role in the event of lineage switch.