CRIP1 functions as an oncogene in acute myeloid leukemia by modulating glycolytic metabolic reprogramming

Acute Myeloid leukemia (AML) is a stem cell-derived hematological malignancy associated with rapid progression and poor clinical outcome despite available treatments. CRIP1 exhibits tissue-specific activity, functioning as an oncogene in certain cancers while acting as a tumor suppressor in others. However, the role of CRIP1 and its association with metabolism in AML remains poorly investigated. To assess its metabolic role, a lactate release and a glucose consumption assay were performed, followed by gene expression analysis of LDHA, MCL1, and HK2 after CRIP1 knockdown. These results were confirmed through Western blot analysis. The CRIP1 knockdown and control cells were treated with 2-DG, a glycolytic inhibitor, and cell death was quantified using flow cytometry. The results showed a significant reduction in the proliferation of AML cells compared to the control, suggesting its oncogenic function. Elevated protein expression of Hexokinase 2, MCL1, and LDHA, suggests CRIP1’s involvement in regulating the glycolytic pathway. CRIP1 knockdown increased glycolytic dependence, and treatment with 2-deoxy-D-glucose (2-DG) selectively induced marked cell death in CRIP1-deficient cells, demonstrating that loss of CRIP1 renders AML cells highly susceptible to glycolytic inhibition. Treatment with 2-DG reduced glucose consumption and lactate production, consequently lowering cellular energy availability and inducing increased cell death. This study reveals a novel role for CRIP1 in AML progression through the modulation of glycolytic biomarkers, highlighting its potential as a therapeutic target.