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Genome-wide expression profiling of CUTTL1 cells upon miR-17-92 cluster overexpression with or without gamma-secretase inhibitor treatment

ABSTRACT: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive T-cell malignancy characterized by genotypically-defined and phenotypically divergent cell populations, governed by adaptive landscapes. Clonal expansions are associated to genetic and epigenetic events, and modulation of external stimuli that affect the hierarchical structure of subclones and support the dynamics of leukemic subsets. Recently, extracellular vesicles (EVs) such exosomes were also shown to play a role in leukemia. Here, we explored the role of EVs in the realm of Notch-driven T-ALLs and found that T-ALL cells secrete Notch-dependent EVs containing microRNAs (EV-miRs), which control oncogenic pathways acting as autocrine stimuli and promote in vitro the expansion/survival of cell subsets of human T-cell leukemias. Of interest, the highlighted Notch-dependent EV-miRs mostly comprised members of miR-17-92a cluster and paralogues, which rescued in vitro the proliferation of T-ALL cells induced by γ-secretase inhibitors (GSI). Additionally, single-cell RNA sequencing analysis of leukemia cells from primary T-ALL patients revealed cell subsets differently responsive to Notch-dependent EV-miRs. All these findings suggest that restricted EV-miRs may sustain the growth/survival of immunophenotypically defined cell populations, altering the cell heterogeneity and the dynamics of T-cell leukemias in response to conventional therapies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE193482 | GEO | 2022/12/28

REPOSITORIES: GEO

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