Myeloid/natural killer (NK) cell precursor acute leukemia as a distinct leukemia type
Menée à partir de l'analyse multiomique d'échantillons de leucémies aiguës à précurseurs myéloïdes ou NK (MNKPL), cette étude met en évidence des caractéristiques moléculaires qui diffèrent de celles des autres leucémies (leucémie myéloïde aiguë, leucémie lymphoblastique aiguë à lymphocytes T et leucémie aiguë de phénotype mixte) ainsi qu'une sensibilité à la L-asparaginase
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. MNKPL is a distinct leukemia subtype, and alterations in key molecules involved in NK cell development have been identified.
Science Advances , article en libre accès, 2022