a novel marker associated with poor pediatric AML outcomes that affect the fatty acid synthesis and cell cycle pathways.

INTRODUCTION

Despite remarkable progress in Pediatric Acute Myeloid Leukemia (pAML) treatments, the relapsed disease remains difficult to treat, making it pertinent to identify novel biomarkers of prognostic/therapeutic significance.

MATERIAL AND METHODS

Bone marrow samples from 21 pAML patients were analyzed using single cell RNA sequencing, functional assays with knockdown and overexpression were performed in leukemia cell lines to evaluate impact on proliferation and migration, and chemotherapy sensitivity. Mitochondrial function was assessed via Seahorse assay, interacting proteins were studied using co-immunoprecipitation. Bulk RNA-seq was performed on knockdown and over expressing cell lines to evaluate the pathways and networks impacted by .

RESULTS

Our data shows that , a novel cancer-associated gene, is highly expressed in the malignant blast cells of multiple pediatric hematologic malignancies, including AML, T/B-ALL, and T/B-MPAL. Notably, expression is significantly elevated in blast cells of patients who relapsed or have a high-risk cytogenetic profile (MLL) compared to standard-risk (). expression is also significantly correlated with the pediatric leukemia stem cell score of 6 genes (LSC6) associated with poor outcomes. Perturbation of (knockdown and overexpression) in leukemia cell lines significantly impacted cell proliferation and migration. The RNA-sequencing analysis on multiple knockdown and overexpressing cell lines established an association with mitochondrial fatty acid synthesis and cell cycle pathways.The investigation of the mitochondrial matrix shows that pharmacological inhibition of a key enzyme in fatty acid synthesis regulation, , resulted in downregulation. knockdown also led to a significant reduction in and ATP production as well as Oxygen Consumption Rate. Our data indicates that downregulating impacts cell proliferation by reducing key cell cycle regulators such as and . Further, we also established that is a key physical interactant of , associated with multiple cancers.

CONCLUSION

Our findings underscore further evaluation of as a potential candidate for targeted therapies and stratification of aggressive pAML to improve outcomes.