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Hematologic malignancies are the most common hematopoietic diseases and a major public health concern. However, the mechanisms underlying myeloid tumors remain unknown owing to the intricate interplay between mutations and diverse clonal evolution patterns, as evidenced by the analysis of bulk cell‐derived omics data. Several single‐cell omics techniques have been used to characterize the hierarchies and altered immune microenvironments of hematologic malignancies. The comprehensive single‐cell atlas of hematologic malignancies provides novel opportunities for personalized combinatorial targeted treatments, avoiding unwanted chemo‐toxicity. In the present study, we performed transcriptome sequencing by combining single‐cell RNA sequencing (scRNA‐seq) with a targeted oncogenic gene panel for acute myeloid leukemia, overcoming the limitations of scRNA‐seq in detecting oncogenic mutations. The distribution of oncogenic IDH1, IDH2, and KRAS mutations in each cell type was identified in the bone marrow (BM) samples of each patient. Our findings suggest that ferroptosis and metabolic reprogramming are involved in the tumorigenesis and chemotherapy resistance of oncogenic mutation‐carrying cells. Biological progression via IDH1, IDH2, and KRAS mutations arrests hematopoietic maturation. Our study findings provide a rationale for using primary BM cells for personalized treatment in clinical settings. Significance statement: The co‐occurrence of mutations in leukemia cells poses challenges in comprehending the occurrence and progression of leukemia, thereby impeding the adoption of personalized therapeutic approaches. By employing transcriptome sequencing that integrates single‐cell RNA sequencing with a targeted oncogenic gene panel, it becomes possible to identify oncogenic mutations at the individual cell level. This approach enhances our comprehension of disease heterogeneity, disease evolution, novel targeted treatment possibilities, and resistance to chemotherapy. Additionally, our investigation revealed a correlation between IDH1/2 and KRAS mutations and the processes of ferroptosis and metabolic reprogramming. [ABSTRACT FROM AUTHOR]

A colon tumor, one of the digestive tract malignant tumors, is harmful to human health. A potential new treatment still deserves attention. The development of a new drug needs more resources, including time and expense. Therefore, the old drug with new targets has become a current research hotspot. Fluvoxamine, as an antidepressant, could play an effect on inhibiting 5‐hydroxytryptamine reuptake. In the present research, the antitumor effects and possible mechanisms of fluvoxamine are validated. The results showed that fluvoxamine significantly suppressed the migration and proliferation of tumor cells, and increased the apoptosis in vitro. Additionally, fluvoxamine significantly delays tumor development, and prompts the apoptosis in tumor tissues of mice‐burdened colon tumors in vivo. The tumor suppression might be related with that fluvoxamine inhibits the expression of phosphorylated signal transducer and activator of transcription 3, matrix metalloproteinase 2, and cleaved‐caspase 3. Importantly, fluvoxamine significantly reduces the expression level of programmed cell death ligand 1. This could be a possible reason that treatment with fluvoxamine drives the infiltration of T lymphocytes and M1‐type macrophages in tumor tissues. Taken together, this research suggests that fluvoxamine might be a promising drug to treat colon cancer by inhibiting the proliferation and migration, inducing apoptosis, and even increasing the immune response of antitumor. [ABSTRACT FROM AUTHOR]