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Cellular hierarchy insights reveal leukemic stem-like cells and early death risk in acute promyelocytic leukemia
oleh: Wen Jin, Yuting Dai, Li Chen, Honghu Zhu, Fangyi Dong, Hongming Zhu, Guoyu Meng, Junmin Li, Saijuan Chen, Zhu Chen, Hai Fang, Kankan Wang
Format: | Article |
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Diterbitkan: | Nature Portfolio 2024-02-01 |
Deskripsi
Abstract Acute promyelocytic leukemia (APL) represents a paradigm for targeted differentiation therapy, with a minority of patients experiencing treatment failure and even early death. We here report a comprehensive single-cell analysis of 16 APL patients, uncovering cellular compositions and their impact on all-trans retinoic acid (ATRA) response in vivo and early death. We unveil a cellular differentiation hierarchy within APL blasts, rooted in leukemic stem-like cells. The oncogenic PML/RARα fusion protein exerts branch-specific regulation in the APL trajectory, including stem-like cells. APL cohort analysis establishes an association of leukemic stemness with elevated white blood cell counts and FLT3-ITD mutations. Furthermore, we construct an APL-specific stemness score, which proves effective in assessing early death risk. Finally, we show that ATRA induces differentiation of primitive blasts and patients with early death exhibit distinct stemness-associated transcriptional programs. Our work provides a thorough survey of APL cellular hierarchies, offering insights into cellular dynamics during targeted therapy.