Myeloid/natural killer (NK) cell precursor acute leukemia as a distinct leukemia type.
Akira NishimuraKazuaki YokoyamaTakuya NarutoChika YamagishiToshihiko ImamuraHiroto NakazonoShunsuke KimuraMieko ItoMaiko SagisakaYukie TanakaJinhua PiaoYui NamikawaMasakatsu YanagimachiTakeshi IsodaAkinori KanaiHirotaka MatsuiTomoya IsobeAiko Sato-OtsuboNaoko HiguchiAkiko TakadaHaruna OkunoShoji SaitoShuhei KarakawaShogo KobayashiDaisuke HasegawaHiroyuki FujisakiDaiichiro HasegawaKazutoshi KoikeTakashi KoikeShinya RaiKatsutsugu UmedaHideki SanoKanako Mitsui-SekinakaAtsushi OgawaAkitoshi KinoshitaNorio ShibaMizuka MikiFumihiko KimuraHideki NakayamaYozo NakazawaTakashi TagaTomohiko TakiSouichi AdachiAtsushi ManabeKatsuyoshi KohYasushi IshidaJunko TakitaFumihiko IshikawaHiroaki GotoTomohiro MorioShuki MizutaniArinobu TojoMasatoshi TakagiPublished in: Science advances (2023)
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.
Keyphrases
- nk cells
- acute myeloid leukemia
- single cell
- induced apoptosis
- bone marrow
- acute lymphoblastic leukemia
- allogeneic hematopoietic stem cell transplantation
- dendritic cells
- cell cycle arrest
- high throughput
- rna seq
- randomized controlled trial
- transcription factor
- endoplasmic reticulum stress
- cell proliferation
- signaling pathway
- immune response
- clinical practice
- drug induced