GENE EXPRESSION OF RHOC GTPASE IS INCREASED IN ACUTE MYELOID LEUKEMIA PATIENTS WITH INACTIVATION OF THE P53 SIGNALING PATHWAY

Abstract

Background: Acute myeloid leukemia (AML) is aa severe hematological malignancy characterized by the expansion of immature myeloid cells in the bone marrow. The p53 signaling pathway is altered in AML, impacting disease progression. Rho GTPase proteins contribute to cellular processes regulated by p53. Aims: Investigate the relationship between RhoA, RhoB and RhoC GTPases gene expression and the activation of p53 pathway in AML. Methods: Data from the AML TCGA study was analyzed. Comparisons were performed in patients classified into two groups (with or without inactivation of p53 signaling) based on cytogenetic data, presence of TP53 mutations and lower or higher expression of TP53, MDM2, MDM4 and CDKN2A. Results: Among the 173 patients, 57 patients were classified as presenting inactivation of the p53 signaling according to our criteria. These patients presented a 3-year overall survival (OS) of 30% compared to a 3-year OS of 23% of patients included in the group without inactivation of p53 signaling (P = 0.0065). Patients with alteration in only one parameter presented a similar OS compared to patients with alterations in 2 or more parameters. Dowregulation of MDM2 was the only parameter that did not occur simultaneouly to the other parameters. Interestingly, RhoC gene expression was increased (0.02950, -1.057 - 4.338) in patients with inactivation of p53 signaling compared to patients without inactivation of p53 signaling (-0.3776, -0.9716 - 5.189) (P = 0.0021). RhoA and RhoC expressions did not differ between the two groups. Conclusion: RhoC expression may be associated with the status of p53 signaling in acute myeloid leukemia. Funding: CAPES.