Convergence of oncogenic cooperation at single-cell and single-gene levels drives leukemic transformation.

ABSTRACT: Cancers develop from the accumulation of somatic mutations, yet it remains unclear how oncogenic lesions cooperate to drive cancer progression. Using a mouse model harboring NRas^G12D and EZH2 mutations that recapitulates leukemic progression, we employ single-cell transcriptomic profiling to map cellular composition and gene expression alterations in healthy or diseased bone marrows during leukemogenesis. At cellular level, NRas^G12D induces myeloid lineage-biased differentiation and EZH2-deficiency impairs myeloid cell maturation, whereas they cooperate to promote myeloid neoplasms with dysregulated transcriptional programs. At gene level, NRas^G12D and EZH2-deficiency independently and synergistically deregulate gene expression. We integrate results from hi

SUBMITTER: Liu Y 

PROVIDER: S-EPMC8566485 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature