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Myeloid/natural killer (NK) cell precursor acute leukemia as a distinct leukemia type.


ABSTRACT: Myeloid/natural killer (NK) cell precursor acute leukemia (MNKPL) has been described on the basis of its unique immunophenotype and clinical phenotype. However, there is no consensus on the characteristics for identifying this disease type because of its rarity and lack of defined distinctive molecular characteristics. In this study, multiomics analysis revealed that MNKPL is distinct from acute myeloid leukemia, T cell acute lymphoblastic leukemia, and mixed-phenotype acute leukemia (MPAL), and NOTCH1 and RUNX3 activation and BCL11B down-regulation are hallmarks of MNKPL. Although NK cells have been classically considered to be lymphoid lineage-derived, the results of our single-cell analysis using MNKPL cells suggest that NK cells and myeloid cells share common progenitor cells. Treatment outcomes for MNKPL are unsatisfactory, even when hematopoietic cell transplantation is performed. Multiomics analysis and in vitro drug sensitivity assays revealed increased sensitivity to l-asparaginase and reduced levels of asparagine synthetase (ASNS), supporting the clinically observed effectiveness of l-asparaginase.

SUBMITTER: Nishimura A 

PROVIDER: S-EPMC10848711 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Myeloid/natural killer (NK) cell precursor acute leukemia as a distinct leukemia type.

Nishimura Akira A   Yokoyama Kazuaki K   Naruto Takuya T   Yamagishi Chika C   Imamura Toshihiko T   Nakazono Hiroto H   Kimura Shunsuke S   Ito Mieko M   Sagisaka Maiko M   Tanaka Yukie Y   Piao Jinhua J   Namikawa Yui Y   Yanagimachi Masakatsu M   Isoda Takeshi T   Kanai Akinori A   Matsui Hirotaka H   Isobe Tomoya T   Sato-Otsubo Aiko A   Higuchi Naoko N   Takada Akiko A   Okuno Haruna H   Saito Shoji S   Karakawa Shuhei S   Kobayashi Shogo S   Hasegawa Daisuke D   Fujisaki Hiroyuki H   Hasegawa Daiichiro D   Koike Kazutoshi K   Koike Takashi T   Rai Shinya S   Umeda Katsutsugu K   Sano Hideki H   Sekinaka Yujin Y   Ogawa Atsushi A   Kinoshita Akitoshi A   Shiba Norio N   Miki Mizuka M   Kimura Fumihiko F   Nakayama Hideki H   Nakazawa Yozo Y   Taga Takashi T   Taki Tomohiko T   Adachi Souichi S   Manabe Atsushi A   Koh Katsuyoshi K   Ishida Yasushi Y   Takita Junko J   Ishikawa Fumihiko F   Goto Hiroaki H   Morio Tomohiro T   Mizutani Shuki S   Tojo Arinobu A   Takagi Masatoshi M  

Science advances 20231213 50


Myeloid/natural killer (NK) cell precursor acute leukemia (MNKPL) has been described on the basis of its unique immunophenotype and clinical phenotype. However, there is no consensus on the characteristics for identifying this disease type because of its rarity and lack of defined distinctive molecular characteristics. In this study, multiomics analysis revealed that MNKPL is distinct from acute myeloid leukemia, T cell acute lymphoblastic leukemia, and mixed-phenotype acute leukemia (MPAL), and  ...[more]

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