Genes & genomics · 2026
Integrative transcriptomics defines CD36 as a key regulator of immunometabolic signaling in acute myeloid leukemia.
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Ashaq Muhammad Sameer, Zhou Qian, Li Yanxia, Guo Meiqi, Zhang Shujing, Wang Lingling, Li Zhuoran, Wang Yi, Huang Yufeng, Shi Zhida, Li Yuan, Zhao Baobing
Аннотация
BACKGROUND: Acute myeloid leukemia (AML) is characterized by extensive immunometabolic rewiring that drives leukemic progression and fosters immune evasion.
OBJECTIVE: This study investigates regulatory role of CD36 as an immunometabolic mediator in AML pathogenesis.
METHODS: Integrated bulk transcriptomics, single-cell RNA sequencing, and in-vitro validation were performed. Macrophage co-localization was validated using colorectal cancer (CRC) spatial transcriptomics.
RESULTS: CD36 was identified as a central hub in preserved immunometabolic modules, enriched for TLR signaling, lipid metabolism, antigen-presenting pathways, and cytokine-cytokine receptor interactions. Drug sensitivity analysis revealed that high CD36 expression showed greater sensitivity to venetoclax and GSK626616AC. CD36 drives AML immune cycle and revealed a strong association with AML functional states, including inflammation, differentiation, apoptosis, invasion, quiescence, and hypoxia. Single-cell analysis indicated CD36 upregulation in monocyte and macrophage clusters, facilitating ligand-receptor communication with T cells, which emphasizes CD36's role in shaping immune microenvironment. Spatial transcriptomics analysis of colorectal cancer confirmed a significant CD36-CD68 colocalization in macrophages. CD36 also influenced monocyte to macrophage differentiation in AML cells. CD36 deficiency significantly reduces AML cells' proliferation and leads to G0/G1 phase expansion, accompanied by E2F4/E2F5/RB1 modulation. Hallmark enrichment analysis unveiled that CD36-high expression leukemic cells, CD36 immune signatures, and monocytes/macrophages showed enrichment in key immune and inflammatory pathways, including TNFα/NF-κB, IL6/JAK/STAT3, and IL2/STAT5 signaling, mTORC1 activation, interferon alpha and gamma responses, and reactive oxygen species pathways.
CONCLUSION: Integration of transcriptomics and spatial validation revealed robust CD36-mediated immunometabolic signaling in AML, which further requires comprehensive in-vitro and in-vivo validation.
OBJECTIVE: This study investigates regulatory role of CD36 as an immunometabolic mediator in AML pathogenesis.
METHODS: Integrated bulk transcriptomics, single-cell RNA sequencing, and in-vitro validation were performed. Macrophage co-localization was validated using colorectal cancer (CRC) spatial transcriptomics.
RESULTS: CD36 was identified as a central hub in preserved immunometabolic modules, enriched for TLR signaling, lipid metabolism, antigen-presenting pathways, and cytokine-cytokine receptor interactions. Drug sensitivity analysis revealed that high CD36 expression showed greater sensitivity to venetoclax and GSK626616AC. CD36 drives AML immune cycle and revealed a strong association with AML functional states, including inflammation, differentiation, apoptosis, invasion, quiescence, and hypoxia. Single-cell analysis indicated CD36 upregulation in monocyte and macrophage clusters, facilitating ligand-receptor communication with T cells, which emphasizes CD36's role in shaping immune microenvironment. Spatial transcriptomics analysis of colorectal cancer confirmed a significant CD36-CD68 colocalization in macrophages. CD36 also influenced monocyte to macrophage differentiation in AML cells. CD36 deficiency significantly reduces AML cells' proliferation and leads to G0/G1 phase expansion, accompanied by E2F4/E2F5/RB1 modulation. Hallmark enrichment analysis unveiled that CD36-high expression leukemic cells, CD36 immune signatures, and monocytes/macrophages showed enrichment in key immune and inflammatory pathways, including TNFα/NF-κB, IL6/JAK/STAT3, and IL2/STAT5 signaling, mTORC1 activation, interferon alpha and gamma responses, and reactive oxygen species pathways.
CONCLUSION: Integration of transcriptomics and spatial validation revealed robust CD36-mediated immunometabolic signaling in AML, which further requires comprehensive in-vitro and in-vivo validation.