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Background: Wnt signaling is a critical pathway for the development of acute myeloid leukemia (AML). Some studies have evaluated the expression or methylation of secreted frizzled-related protein 2 (SFRP2) as an antagonist and beta-catenin (β-catenin) as a critical mediator of this pathway. Since we found no comprehensive study on these genes in Iran, we aimed to investigate the status of both SFRP2 expression and methylation, and also β-catenin expression, in conjunction with clinical characteristics, in Iranian patients with de novo non-M3 AML. Methods: The methylation and expression of SFRP2 were determined in 188 patients with primary non-M3 AML and 60 healthy controls, who were referred to Shariati Hospital, Tehran, Iran, between January 2017 and February 2019. The methylation-specific polymerase chain reaction (PCR) and realtime quantitative PCR were used, respectively. The expression of β-catenin was explored via real-time quantitative PCR. Statistical analysis was performed using the Mann-Whitney U test (SPSS software, version 23). A P value of less than 0.05 (2-tailed) was considered significant. Results: SFRP2 mRNA showed a significant decline in the AML group compared with the controls (P<0.001). The hypermethylation of the SFRP2 promoter occurred in 25.5% (48/188) of the cases. SFRP2 expression exhibited a negative correlation with the white blood cell count (P=0.003). The expression of β-catenin increased significantly in the patients in comparison with the controls (P<0001), and a significant difference was observed between the patients, who achieved complete remission and those, who did not (P=0.046). Conclusion: The findings of this study showed that alterations in SFRP2 and β-catenin expression can be used as a potential biomarker for differentiating patients with new non-M3 AML from the controls. Additionally, an evaluation of β-catenin expression may be valuable in predicting complete remission in patients with non-M3 AML. [ABSTRACT FROM AUTHOR]

Acute lymphoblastic leukemia (ALL) is a malignant transformation and proliferation of lymphoid progenitor cells in the bone marrow, blood and extramedullary sites and the second most common acute leukemia in adults. While dose-intensification strategies have led to a significant improvement in outcomes for pediatric patients, the prognosis for the elderly remains very poor. Aberrant or excessive expression of cytokines may be related to the pathogenesis of acute leukemia. TGF-β is a cytokine that plays a role in regulating various cellular processes such as growth, proliferation, and apoptosis. We evaluated the expression of TGF-β mRNA in adults with ALL compared to the control and its relationship with disease-related prognostic factors. Bone marrow specimens were obtained from 90 newly-diagnosed adults with ALL and 33 healthy adults. After immunophenotyping by flow cytometry, RNA was extracted, and RQ-PCR was done. Our result showed that from all patients, 63 (70%) were identified as B-ALL and 27(30%) as T-ALL. TGF-β transcript levels in both T-ALL and B-ALL patients showed a significant decrease compared to the control group (P < 0.001). However, the expression of the TGF-β transcripts was not different between the different immunophenotypic subtypes (P=0.54). The gene expression level of TGF-β was not correlated with age (P=0.47), gender (P=0.29), ALL subtypes (P=0.54), the percentage of bone marrow blasts (P=0.92) and peripheral blood leukocyte count (P=0.38) of ALL patients. In conclusion, since TGF-β has a tumor suppressor role, it seems that leukemic cells may use TGF-β down-regulation to be more freely proliferated and evolve the clone. [ABSTRACT FROM AUTHOR]