AML-069 The Role of Genes Related to the Apoptosis and Neddylation Pathway in Patients With Acute Myeloid Leukemia

• Published in: Clinical lymphoma, myeloma and leukemia Vol. 24; pp. S291 - S292
• Main Authors: Krawiec, Kinga, Strzałka, Piotr, Jarych, Dariusz, Wiśnik, Aneta, kościelny, Kacper, Mikulski, Damian, Czemerska, Magdalena, Zawlik, Izabela, Wierzbowska, Agnieszka, Pluta, Agnieszka
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.09.2024
• Subjects: apoptosis; neddylation; prognosis; regulated cell death; regulated cell death; apoptosis; neddylation; prognosis
• ISSN: 2152-2650
• DOI: 10.1016/S2152-2650(24)01155-8

The prognosis of patients with acute myeloid leukemia (AML) is related to the genetic profile of the disease. Abnormalities in the expression of apoptosis and neddylation genes, responsible for regulated cell death, may contribute to the development and resistance of leukemic cells. Assess the expression and significance of genes regulating apoptosis and neddylation in AML. A prospective study of 86 newly diagnosed AML patients (mean age 66; range 25-80). The expression of BIM, BID, BIK, PUMA, NOXA, BAD, BAX, BAK, BCL2, BCLX, MCL1, SMAC/DIABLO, CASP3, CASP7, TP53, NEDD8, and cullin genes was determined in duplicate in samples from bone marrow using real-time PCR. Normalization was performed by ΔCt = Ct(reference) – Ct(mRNA of interest). The ΔΔCt method was used to calculate fold changes (FC) in mRNA expression. According to European LeukemiaNet 2022 risk stratification, 39.5% of patients in the study group were high-risk, 40.7% intermediate-risk, and 13.9% low-risk AML. Molecular data was not available for 5 patients. Intensive treatment was introduced in 37.2% of patients, while 24.4% were treated with azacitidine + venetoclax and 38.4% with other nonintensive regimens. With a median follow-up of 10.3 months (95% CI, 7.8-14.4), median overall survival (OS) was 12.9 months (95% CI, 6.7-16.1). Significant upregulation of antiapoptotic genes compared to proapoptotic and neddylation genes (FC=11.0, P<.001, FC=2.7, P<.001, respectively) was detected. In univariate Cox regression analysis, BIK expression (hazard ratio [HR]=1.2; 95% CI, 1.01-1.43; P=.041), TP53 expression (HR=0.61; 95% CI, 0.42-0.86; P=.005), initial albumin level (HR=0.33; 95% CI, 0.17-0.62; P=.001), age (HR=1.03; 95% CI, 1.00-1.06; P=.02), and intensive treatment (HR=0.26; 95% CI, 0.12-0.57, P=.001) were factors influencing the outcome. In the multivariate model for OS, higher expression of BIK (HR=1.27; 95% CI, 1.06-1.53, P=.011) retained its significant negative impact, while TP53 maintained the protective effect on OS (HR=0.56; 95% CI, 0.38-0.87; P=.008) in terms of established prognostic factors. Our study revealed apoptosis gene dysregulation and that BIK and TP53 may be potential prognostic factors in AML. Our preliminary results did not prove a significant effect of neddylation gene expression levels on the prognosis of AML patients; thus, further research is needed.