Low expression of MKRN1 promotes leukemia cell proliferation.

BACKGROUND: The MKRN1 gene encodes a specialized E3 ubiquitin ligase with a zinc finger structure, is the ancestor of the MKRN gene family, and is involved in the occurrence and development of colorectal cancer, lung cancer, ovarian cancer, and other malignancies. However, its role in acute lymphoblastic leukemia (ALL) is still unknown. This study aims to explore the function of MKRN1 in ALL. METHODS: The public databases and R package limma were employed to analyze the expression and prognosis of MKRN1 in ALL. Bone marrow aspiration samples were collected from patients to further investigate the mRNA expression levels of the target gene in children with ALL, Lentivirus transduction was employed to knock down and overexpress MKRN1 in two leukemia cell lines (NALM6 and Jurkat), proliferation was measured using the CCK-8 assay, and clinical data were collected for correlation analysis of MKRN1 and clinical characteristics in ALL. RESULTS: Compared to normal children, MKRN1 expression was significantly lower in children with ALL, and low expression of MKRN1 was associated with poor prognosis. The overexpression of MKRN1 inhibited the proliferation of the Jurkat cell line, while knockdown of MKRN1 promoted the proliferation of the NALM6 cell line. The expression level of MKRN1 correlated with risk stratification, initial white blood cell count, hemoglobin and platelet counts, the blast/naïve cell ratio, and minimal residual disease (MRD) on day 19. High expression of MKRN1 was identified as a protective factor for MRD negativity on day 19. CONCLUSION: MKRN1 knockout promotes acute lymphoblastic leukemia cell proliferation; conversely, high MKRN1 expression serves as a positive prognostic factor for favorable early treatment response, establishing MKRN1 as a novel biomarker in ALL.