Transient Differentiation-State Plasticity Occurs during Acute Lymphoblastic Leukemia Initiation.

ABSTRACT: Leukemia is characterized by oncogenic lesions that result in a block of differentiation, whereas phenotypic plasticity is retained. A better understanding of how these two phenomena arise during leukemogenesis in humans could help inform diagnosis and treatment strategies. Here, we leveraged the well-defined differentiation states during T-cell development to pinpoint the initiation of T-cell acute lymphoblastic leukemia (T-ALL), an aggressive form of childhood leukemia, and study the emergence of phenotypic plasticity. Single-cell whole genome sequencing of leukemic blasts was combined with multiparameter flow cytometry to couple cell identity and clonal lineages. Irrespective of genetic events, leukemia-initiating cells altered their phenotypes by differentiation and dedifferentiation.

SUBMITTER: Poort VM 

PROVIDER: S-EPMC11325147 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature