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Extramedullary infiltration (EMI) is a concomitant manifestation that may indicate poor outcome of acute myeloid leukemia (AML). 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 a patient with AML presenting pervasive leukemia cutis. A complement C1Q+ macrophage-like leukemia subset, which was enriched within cutis and existed in BM before EMI manifestations, was identified and further verified in multiple patients with AML. Genomic and transcriptional profiling disclosed mutation and gene expression signatures of patients with EMI that expressed high levels of C1Q. RNA sequencing and quantitative proteomic analysis revealed expression dynamics of C1Q from primary to relapse. Univariate and multivariate analysis demonstrated adverse prognosis significance of C1Q expression. Mechanistically, C1Q expression, which was modulated by transcription factor MAF BZIP transcription factor B, endowed leukemia cells with tissue infiltration ability, which could establish prominent cutaneous or gastrointestinal EMI nodules in patient-derived xenograft and cell line–derived xenograft models. Fibroblasts attracted migration of the C1Q+ leukemia cells through C1Q–globular C1Q receptor recognition and subsequent stimulation of transforming growth factor β1. This cell-to-cell communication also contributed to survival of C1Q+ leukemia cells under chemotherapy stress. Thus, C1Q served as a marker for AML with adverse prognosis, orchestrating cancer infiltration pathways through communicating with fibroblasts and represents a compelling therapeutic target for EMI.

To study the anti-aging effect of astragalosides (AST) and its mechanism of action.Rotating rod test and step-down type passive avoidance test were performed to determine the effects of AST on motor and memory of D-galactose (D-gal)-induced senescent mice and the middle-aged mice. The proliferative response of splenocytes induced by Con A or LPS, IL-2 production of splenocytes induced by ConA of D-gal-treated mice and the middle-aged mice were also measured.AST (40 mg.kg(-1).d(-1), ig, for 10 weeks) was found to ameliorate age-related alternations in both motor response and memory, enhance the deteriorated cellular immunity in D-gal-treated mice and the pre-aged (17-month-old) mice.AST has an anti-aging effect on D-gal-induced senescent mice and has the effect of delaying senility of the middle-aged mice, which was related to its improvement of brain function and immunomodulatory effects.