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  • Küçük Resim Yok
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    Diagnostic and Prognostic Significance of miR-155, miR-181, miR-221, miR-222, and miR-223 Expression in Myelodysplastic Syndromes and Acute Myeloid Leukemia
    (Mdpi, 2025) Ardic, Cemile; Ay, Mustafa Ertan; Cevik, Kenan; Tombak, Anil; Izci Ay, Ozlem; Karakas, Umit; Erdal, Mehmet Emin
    Background: Myelodysplastic syndromes (MDSs) and acute myeloid leukemia (AML) are clonal hematological disorders that share molecular origins but present with distinct clinical features. MicroRNAs (miRNAs) are key post-transcriptional regulators, and their altered expression may reflect biological shifts contributing to disease progression. Methods: Expression levels of miR-155, miR-181, miR-221, miR-222, and miR-223 were analyzed by RT-qPCR in bone marrow samples from 37 MDS patients, 20 AML patients, and 7 controls. Group comparisons were performed using ANOVA (with Benjamini-Hochberg correction) and Tukey post hoc testing. Diagnostic performance and network behavior were evaluated using ROC analysis, Pearson correlation matrices, and principal component analysis (PCA). Results: miR-155, miR-181, and miR-223 were upregulated in AML, whereas miR-221 and miR-222 were downregulated. miR-222 showed the highest diagnostic accuracy (AUC similar to 0.87 for both AML vs. control and MDS vs. control). Its expression was significantly higher in high IPSS-R MDS cases (p = 0.046), with a similar upward tendency for miR-221 (p = 0.054). Progressive loss of coordinated miRNA expression was observed from controls to MDS and AML. PCA supported these findings by showing separation mainly driven by miR-222 and miR-155. Conclusions: Combined miRNA profiling highlights miR-222 and, to a lesser extent miR-155, as consistent indicators of myeloid disease transformation. While further validation in larger and genetically stratified cohorts is warranted, these findings support the potential contribution of miRNA signatures to diagnostic evaluation and risk stratification in MDS and AML, in line with precision hematology approaches.
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    Disrupted miRNA Biogenesis Machinery Reveals Common Molecular Pathways and Diagnostic Potential in MDS and AML
    (Mdpi, 2025) Cevik, Kenan; Ay, Mustafa Ertan; Tombak, Anil; Ay, Ozlem Izci; Karakas, Umit; Erdal, Mehmet Emin
    Background: Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are clonal stem cell disorders in which disrupted post-transcriptional regulation contributes to aberrant hematopoiesis and leukemic transformation. The miRNA biogenesis machinery, which comprises Drosha, DGCR8, Dicer, TARBP2, and AGO1, ensures the precise maturation of miRNAs that control lineage commitment and proliferation. However, the extent to which alterations in this pathway reshape hematopoietic gene networks during myeloid disease evolution remains largely unexplored. Methods: Bone marrow samples from newly diagnosed, untreated MDS and AML patients and matched healthy controls were analyzed for the expression of five key miRNA biogenesis genes using quantitative real-time PCR. Statistical comparisons, correlation matrices, and ROC analyses were performed to characterize gene-expression differences. These results were integrated with multigene logistic modeling, decision-curve analysis, and exploratory random forest/SHAP approaches to evaluate molecular interactions and diagnostic relevance. Results: DROSHA, DICER1, and TARBP2 were significantly downregulated in both MDS and AML, suggesting impaired miRNA maturation and a loss of global post-transcriptional control. DGCR8 expression increased across higher-risk MDS groups, suggesting compensatory activation of the Microprocessor complex, whereas AGO1 levels remained relatively stable, consistent with partial maintenance of RISC function. Correlation analyses revealed a co-regulated DROSHA-TARBP2-AGO1 module. ROC, logistic, and machine learning models identified DGCR8 and DICER1 as the strongest diagnostic discriminators. The integrated five-gene signature achieved high discriminative performance (AUC approximate to 0.98) and showed promise but remains preliminary potential for clinical application. Conclusions: Our findings suggest that defects in miRNA biogenesis disrupt hematopoietic homeostasis, reflecting common mechanisms in MDS and AML. The dysregulation of DICER1, DGCR8, and TARBP2 offers insights into miRNA-driven leukemogenesis and may pave the way for miRNA-based diagnostic and therapeutic strategies, pending validation in larger cohorts. Although transcript-level data are provided, future studies should include functional validation to determine the impact on downstream miRNA processing and hematopoietic pathways.
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    Majör depresyon hastalarında BDNF gen polimorfizmi (rs6265) ile BDNF gen ekspresyon düzeylerinin araştırılması
    (2023) Karakas, Ümıt; Çevik, Kenan; Ay, Mustafa Ertan; Özdemir, Gurbet Doğru; Zıblak, Alper; Kenar, Ayse Nur Inci; Erdal, Mehmet Emin
    Amaç: Beyin kaynaklı nörotrofik faktörün (BDNF) genetik, moleküler ve hücresel mekanizmalarının ve bunun nöroplastisite ile ilişkisinin daha iyi anlaşılması, majör depresyonda (MD) yeni ilaçlar için gelecekteki terapötik hedeflerin bulunmasında çok önemli bir rol oynayabilir. Bu çalışma, BDNF polimorfizmlerinin MD'deki kesin rolüne ilişkin hala çelişkili sonuçlar olduğundan, MD'de BDNF ile ilişkili polimorfizm (rs6265) ve ekspresyon ilişkisini anlamak amacıyla planlandı. Yöntem: Bu olgu-kontrol çalışmasında, DSM-5 ölçütlerine göre MD’li 51 hasta ve 75 sağlıklı kontrole ait kanlardan BDNF gen Val66Met (rs6265) polimorfizmleri için dizayn edilmiş primerler ile Real-Time PCR ile tek nükleotid polimorfizm çalışmaları yapıldı. Gen ekspresyon analizleri için total RNA kullanıldı. Kantitatif Real-Time PCR yöntemi ile saptanan, MD ve kontrol gruplarındaki BDNF genine ait ekspresyon düzeyleri ile polimorfizmler arasındaki ilişki istatistiksel yöntemlerle incelendi. Bulgular: Erkek ve kadınlarda, genotip ile grup ve alel frekansı ile grup arasında istatistiksel olarak anlamlı bir ilişki gözlenmemiştir. Alel ile MD arasındaki ilişkide ve genotip ile MD arasında anlamlı bir ilişki olmadığı görülmüştür. Genotip grupları arasında BDNF ekspresyon düzeyleri bakımından istatistiksel olarak anlamlı bir farklılık yoktur. Hem MD grubu hem de kontrol grubu için BDNF’nin polimorfik genotipleri arasında ekspresyon düzeyleri bakımından fark gözlenmemiştir. Sonuç: Çalışma bulguları istatistiksel olarak önemli olmamasına rağmen rapor edilmiş önceki çalışmaların da ışığında BDNF varyantlarının daha derinlemesine analizlerinin, gelecekte farmasötik müdahale ve majör depresyonun hassas tıbbı için olası yeni hedeflere işaret edebileceğini düşünmekteyiz. Ayrıca kişiselleştirilmiş tıp çağında, klinik müdahalelerin etkinliğini etkileyebilecek hem küresel hem de spesifik faktörlerin anlaşılması, tıp alanında önemli ilerlemeler sağlayabilir
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    Short-Term Effects of Extremely Low-Frequency Electromagnetic Fields on Neurogenesis and Wnt Signaling in Amniotic Fluid Cells
    (Necmettin Erbakan Univ, Fac Medicine-Neu Press, 2025) Uzun, Cosar; Karakas, Umit; Ay, Mustafa Ertan; Ay, Ozlem Izci; Yildiri, Didem Derici; Erdal, Nurten; Erdal, Mehmet Emin
    Background: Extremely low-frequency electromagnetic fields (ELF-EMF) at 50 Hz are prevalent in household electrical systems. Although various studies have examined the effects of ELF-EMF on cell proliferation and gene expression, its impact on amniotic fluid cells (AFCs) remains unclear. Objectives: This study aimed to assess the potential effects of ELF-EMFs on gene expression related to neurogenesis and the Wnt signaling pathway in AFCs. Methods: AFCs were isolated from amniotic fluid obtained via amniocentesis and divided into five groups: control, sham, and three groups exposed to different ELF-EMF intensities (1 mT, 2 mT, 3 mT for 30 minutes/day for 7 days). Expression levels of genes involved in neurogenesis (HES1, Neurog1, Neurog2, Neurod1) and Wnt signaling (SFRP2, SFRP4, SFRP5, APC1) were analyzed using real-time PCR. Results: ELF-EMF exposure did not result in significant changes in gene expression among the experimental groups compared to controls. Conclusion: Short-term exposure (Acute exposure) to ELF-EMF at moderate intensities does not significantly impact gene expression related to neurogenesis or Wnt signaling in AFCs. Future studies should explore prolonged exposure (chronic exposure) and a broader range of intensities to evaluate developmental impacts more comprehensively.