Global protein expression profiling in stem cell factor stimulated human Acute megakaryoblastic leukemia cells identifies CFL1, GSN and CCT8 as prognostic biomarkers for Acute Myeloid Leukemia.

A study has discovered three key proteins associated with Acute Myeloid Leukemia (AML) that could serve as prognostic biomarkers. The research focused on the stem cell factor (SCF) receptor, c-Kit, which triggers signaling pathways impacting blood cell proliferation, survival, differentiation, and migration. These pathways are believed to contribute to AML development and progression.

Human Acute megakaryoblastic leukemia (Mo7e) cells were treated with SCF, and their global protein expression was analyzed through two-dimensional gel electrophoresis combined with MALDI-TOF and LC-MS/MS. The study identified 14 differentially expressed proteins, which are predicted to be involved in various cellular processes such as cytoskeletal organization, protein folding, metabolism, vesicular trafficking, and translational regulation.

Further investigation of the TCGA-LAML cohort revealed significant alterations in the expression of CFL1, CCT8, HSP90B1, MDH2, EIF5A, GSN, and TPI1. By combining ROC, Cox regression, and LASSO analyses, the researchers found CFL1, CCT8, and GSN to be the most reliable prognostic biomarkers associated with poor overall survival in AML patients. The expression patterns of these genes were confirmed in other independent GEO datasets and validated through quantitative RT-PCR in SCF-stimulated Mo7e cells.

To aid in predicting the overall survival probability of AML patients, the scientists developed a three-gene nomogram model based on CFL1, CCT8, and GSN. This model was also validated and can be used to estimate the likelihood of survival at 1-, 3-, and 5-year time points. This discovery not only provides new insights into the mechanisms of c-Kit-driven leukemogenesis but also offers a clinically relevant three-gene signature for AML risk stratification and potential therapeutic targeting.