Transcriptomics

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RNA sequencing for AML patients with and without extramedullary infiltration


ABSTRACT: Extramedullary infiltration (EMI) is a concomitant manifestation indicating poor prognosis of acute myeloid leukemia (AML), yet the underlying mechanism remains poorly understood and therapeutic options are limited. Here, we employed single-cell RNA sequencing on bone marrow (BM) and EMI samples from an AML patient presenting pervasive leukemia cutis. A complement C1Q+ macrophage-like leukemia subset which is enriched within cutis and existed in BM prior to EMI manifestations was identified and further verified in multiple AML patients. RNA-sequencing and quantitative proteomics profiling revealed adverse prognosis of patients bearing C1Q+ population. C1Q expression endowed leukemia cells with tissue-infiltration ability which could establish prominent cutaneous or gastrointestinal EMI nodules in patient-derived xenograft (PDX) and CDX models. Fibroblasts attracted migration of the C1Q+ leukemia cells through surface C1Q-gC1QR recognition and subsequent stimulation of MAFB5 TGF-β signaling. Thus, C1Q orchestrates cancer infiltration pathways through communicating with fibroblasts and represents a compelling therapeutic target for EMI.

ORGANISM(S): Homo sapiens

PROVIDER: GSE213584 | GEO | 2023/04/07

REPOSITORIES: GEO

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