asuman sunguroglu | Ankara University (original) (raw)

Papers by asuman sunguroglu

Naunyn-Schmiedeberg's archives of pharmacology, Jun 25, 2024

Bu projenin amaci; KML blastik fazda gorulen imatinib mesilat direncliligi uzerineBim ve Bid proa... more Bu projenin amaci; KML blastik fazda gorulen imatinib mesilat direncliligi uzerineBim ve Bid proapoptotik genlerinin etkilerinin arastirilmasidir. Bu sebeple Bim ve Bidgenlerinin epigenetik olarak regule edilip edilmedigi incelenmistir. Bim ve Bid proapoptotikgenlerinin promotor metilasyon durumlari ve bunun uzerine PRC4 kompleks proteinlerininetkileri arastirilmistir.Calismada imatinib mesilat direncli K-562/IMA-3 hucre dizisi ile Đmatinib direncliolmayan K-562 hucre dizilerinde PRC4 kompleksinde yer alan EZH2, EED2, SUZ12,SIRT1 genleri ile proapoptotik genler olan Bim ve Bid’in mRNA seviyeleri belirlenmistir.H3K27 uclu metilasyonu yapan EZH2’nin, Bim ve Bid genlerine baglanip baglanmadiklarive bu genlerin H3K27 uclu metilasyon modifikasyonu ChIP deneyi ile arastirilmistir. Dahaonce yapilan calismalar ile ozellikle EZH2 ve SIRT1’in baglandigi bolgeye DNMTenzimlerini cekme yolu ile ilgili genlerin promotor metilasyonuna yol actigi ve genifadelerini epigenetik olarak susturdugu gosterildiginden, Bim ve Bid genlerinin metilasyondurumu MSP-PZR ile belirlenmistir. Ayrica her iki hucre dizisinin tasidigi sitogenetikanomaliler Giemsa bantlama (GTG) metodu ile belirlenmis ve karsilastirilmistir.Arastirma sonunda PRC4 grubuna ait proteinlerin iki hucre hattinda da ifade edildigies-zamanli PZR ile belirlendi. Ancak beklenilenin tersine K-562/IMA-3 hucrelerindeImatinib duyarli olan K-562 hucrelerine gore PRC4 genlerinin ifadeleri daha dusuk, Bim veBid genlerinin ifadeleri ise daha yuksek bulundu.ChIP deneyleri sonucunda ise her iki hucre hattinda Bim geninin promotorununkromatin bolgesinde PRC4 protein grubu uyesi olan EZH2 enziminin ve DNMT1 enzimininbagli oldugu bulundu. Ayrica her iki hucre hattinda EZH2 tarafindan yapildigi dusunulenH3K27me3 modifikasyonu da belirlendi. Imatinib duyarli K-562 hucrelerinde yapilan ChIPdeneyleri sonucunda ise Bid geni promotor bolgesine EZH2 ve DNMT1 enzimleri baglibulundu ve Bid promotorunda H3K27me3 modifikasyonu tespit edildi.Imatinib mesilat direnci gelistirilmis K-562/IMA-3 hucrelerinde ise Bid genipromotoruna EZH2 ve DNMT1 enzimleri bagli bulunmadi. Ve genin kromatin bolgesindeise H3K27me3 modifikasyonunu tespit edildi. Bir diger ChIP deneyi sonucuna gore iseImatinib mesilat direnci gelistirilmis K-562/IMA-3 hucrelerinde Bim geninin promotorunaEZH2 ve DNMT1 bagli bulundu. ve H3K27me3 modifikasyonu tespit edildi. Yapilan MSPZRdeneyleri sonucunda ise Bim ve Bid genlerinin promotor bolgesi homozigot olarakmetillenmemis bulundu.Bu arastirmada yapilan deneyler sonucunda Imatinib mesilat direnci gelistirilmis K-562/IMA-3 hucre hattinda ilac direncliliginde rol oynadigini dusundugumuz apoptoz direncinde Bim ve Bid genlerinin epigenetik olarak modifiye edilmelerine ragmen direktolarak bir rol oynamadigini soyleyebiliriz. AbstractThe aim of this study is to investigate the effects of the Bim and Bid proapoptoticgenes on Imatinib mesilat resistance in which seen CML blastic phases. For this purpose, itwas investigated that whether Bim and Bid genes are regulated as epigenetically. Thepromoter methylation status of the Bim and Bid proapoptotic genes and the effects of thePRC4 protein complex on it were investigated.In this study, mRNA levels of EZH2, EED2, SUZ12, SIRT1 genes which belongs toPRC4 complex and Bim and Bid proapoptotic genes were determined in the Imatinibmesilate resistant K-562/IMA-3 cell lines and the non-resistant K-562 cell lines.Additionally, whether EZH2 protein which cause H3K27 trimethylation bind to Bim and Bidgenes or not and H3K27 trimethylation modification of this genes were searched by ChIPassays.It was shown that the EZH2 and SIRT1 may cause promotor methylation of relatedgenes via taking the enzyme of the DNMT to its bounded region and cause to silence of thegenes as epigenetically in the previous studies. For that reason the methylation status of theBim and Bid genes were determined by specific PCR technique. Cytogenetic anomalies ofthe cell lines were determined by the Giemsa banding tecnique (GTG) and compared witheach other.It was detected that the proteins that belong to group of the PCR4 expressed in theboth cell lines by the real time PCR technique. Despite to our expectation the expression ofthe PRC4 genes were deteced at lower level and the expression of the Bim and Bid geneswere detected at higher lever in the K-562/IMA-3 cells than imatinib non-resistant K-562cells.It was founded from CHIP experiment that the E2H2 enzyme which is belong toPRC4 protein family bounded to the DNMT1 enzyme in the promoter region of the BĐDgenes in the both cell lines. Furthermore, the modification of H3K27me3, thought inducedby the EZH2 have been detected in the both cell lines. Additionally the modification of theH3K27me3 in the promoter region of Bid genes and linkage between the EZH2 and DBNT1enzymes and the promoter region of the the Bid was detected at the end of the study.The EZH2 and DNMT1 enzymes were not founded as bounded to the promoter regionof the Bid…

Türkiye fiziksel tıp ve rehabilitasyon dergisi, 2016

ER stresi cesitli tetikleyicilere karsi cevap olarak olusur. Cesitli fizyolojik ve patolojik kosu... more ER stresi cesitli tetikleyicilere karsi cevap olarak olusur. Cesitli fizyolojik ve patolojik kosullar ER’ da katlanmamis ya da yanlis katlanmis proteinlerin birikmesine sebep olur. Bunun sonucunda Katlanmamis Protein Cevabi (KPC) tetiklenir ve hucre ici sinyal iletim yolaklari kullanilarak stres asilmaya calisilir. ER stresi asilamaz ya da stres uzun sure devam ederse, ER stresi apoptozu aktive eder. Yapilan calismalar ER stresinin indukledigi otofajinin yogun ve devam eden ER stresine karsi koruyucu bir rol oynadigi gostermektedir. Pankreatik beta hucrelerinde insulin uretimi fazla oldugundan ER’lerinde oldukca fazla yuk vardir. Bu neden ile pankreatik beta hucreleri ER stresine karsi oldukca hassastir. ER stresi kosullarinda aktif hale gelen ATF6’nin aktivasyon mekanizmasi konusunda az sayida calisma bulunsa da insulin salgilayan pankreatik β hucrelerindeki ATF6 yolagini aciklayan bir mekanizma tam olarak rapor edilmemistir. Pankreatik β Hucrelerinin endoplasmik retikulum stre...

The Turkish Journal Of Occupational / Environmental Medicine and Safety, Feb 16, 2017

Nowadays according to the increased prevalence of metabolic disorders such as diabetes and obesit... more Nowadays according to the increased prevalence of metabolic disorders such as diabetes and obesity, there is an increasing trend of consumption of non-caloric foods and drinks. As a result of this situation there is a widely use of the extracts of a natural plant, Stevia rebaudiana, or its compounds as a sweetener. In this study, it was aimed to investigate possible toxixological effects of stevia and its oxidative compounds on an oxidant parameter in liver tissue from rats. For this aim, 26 adult Wistar type albino rat were used in the study. The animals were divided into two groups as the control group (n=10) and the study group (n=16) randomly. While the control group (Group 1) was fed only by standard rat diet, the study group (Group 2) was fed by standard rat diet with a sweetener including 22 mg stevia extract per day aurogastricly for one month. At the end of the study, rats were sacrified and the liver tissues were surgically removed to analyze an oxidant parameter which is Malondialdehyde-MDA levels. And also histopathological examination and tissue DNA extraction were done. According to the results of the study in liver tissues, MDA levels of the study group which were fed by stevia extract were found significantly higher than that in the control group (p=0,021). The tissues of the group 2 displayed some histopathological changes such as remarkable dilatation of sinusoids. There were no histopathological changes in the structure of hepatocytes and also we did not observe any apoptotic or necrotic cell and histopathological changes in the portal area, except the cellular infiltration in a few focal portal areas. There was no difference between groups according to DNA extraction findings. According the data of MDA levels and histopathological findings, it was thought that the consumption of high dose of stevia as a sweetener may cause oxidant effects on liver tissues.

Smoking poses a serious threat to public health. The aim of this study was to investigate the rel... more Smoking poses a serious threat to public health. The aim of this study was to investigate the relationship between smoking and DNA damage in lymphocytes. A potential genotoxic effect of cigarette smoking was analyzed with the nine comet assay parameters including comet length (CL), comet intensity (CI), head length (HL), head intensity (HI), tail length (TL), tail intensity (TI), DNA tail (DNAt), tail moment (TM) and olive tail moment (OTM). For the first time in this study, smokers were grouped as female and male, and nine comet parameters were used. Material and Method: 120 volunteers (60 non-smokers, 60 smokers) were monitored in the way of DNA damage in blood lymphocytes. The levels of DNA damage was measured by BAB Bs Comet Assay system. Results: Highly significant associations were found between the non-smoker and smoker groups for CI, TL and OTM comet parameters (p<0.01). Smoker female group had higher CL, CI, HL, HI, TL, TI (p<0.01) and TM (p<0.05) with regard to DNA damages than the non-smoker female group. In contrast, only DNAt, and OTM comet parameters were statistically significantdifferences between the smoker male and non-smoker male groups (p<0.05). When the smoking index (SI) of all the blood samples from females were compared based on all studied comet parameters, statistically significant association was found except for TM. On the other hand, the blood samples taken from males were statistically significant in terms of CL, HL, HI, TI and OTM parameters (p<0.05). Conclusion: Consequently, it can be said that, smoking cause DNA damages and females are more sensitive to the effect of the smoking than males.

Molecular Biology Reports, Dec 14, 2022

Zeitschrift für Naturforschung C, Mar 1, 2015

A series of novel 5-(4-methylpiperazin-1-yl)-2-phenyl-1H-benzimidazoles (5-14) were synthesized a... more A series of novel 5-(4-methylpiperazin-1-yl)-2-phenyl-1H-benzimidazoles (5-14) were synthesized and evaluated for their in vitro antiproliferative activities against the human leukemia cell line HL-60. Compounds 5-7 and 10-12 exhibited potent antiproliferative activities against this cell line. The quantitative analysis of apoptosis by flow cytometry demonstrated that the percentages of apoptotic HL-60 cells treated with compounds 5 and 10-12 were significantly higher than in the control.

Ankara Üniversitesi Eczacılık Fakültesi dergisi, Sep 27, 2022

Objective: SIRT5 is a mitochondrial protein that removes acetyl, malonyl and succinyl groups from... more Objective: SIRT5 is a mitochondrial protein that removes acetyl, malonyl and succinyl groups from lysine moieties in target proteins and interacts with cytochrome c and causes its deacetylation. There is no study on the effects of SIRT5 in K562 chronic myeloid leukemia cells. Resveratrol and Suramin are known to play a role in modulating the deacetylase and desuccinylase activities of SIRT5. It has been reported that Resveratrol induces apoptosis of K562 cells but effects of Suramin on the apoptosis of K562 cells are largely unknown. In this study, it was aimed to elucidate the effects of SIRT5 modulators Resveratrol and Suramin on proliferation and apoptosis of K562 cells and on SIRT5 and cytochrome c protein, a known target of SIRT5. Material and Method: K562 chronic myeloid leukemia cells were treated with increasing concentrations of suramin and resveratrol, cell proliferation was determined by MTT assay and BrdU incorporation. Apoptosis was determined with Annexin V staining by Flow cytometry. Western Blot analysis was performed to determine the effect of resveratrol and suramin on SIRT5 and Cytochrome c protein expression levels. Result and Discussion: Our results showed that suramin did not affect SIRT5 and cytochrome c protein expressions significantly and resveratrol decreased SIRT5 and increased cytochrome c expression. Suramin did not cause any changes on the apoptosis of K562 cells. Resveratrol decreased cell proliferation and induced

Archives of Pharmacal Research, Jul 18, 2014

A series of novel 2-(4-phenoxyphenyl)-1Hbenzimidazole derivatives was synthesized and tested in v... more A series of novel 2-(4-phenoxyphenyl)-1Hbenzimidazole derivatives was synthesized and tested in vitro on human chronic myelogenous leukemia (CML) cell line K562. Benzimidazoles containing 5-amidino (10), 5-N-isopropylamidino (11), 5-bromo (13), and 5,6-dimethyl (14) derivatives exhibited remarkable cytotoxic activity. The quantitative analysis of apoptosis by flowcytometry demonstrated that the percentages of early and late apoptotic K562 cells treated with these compounds were significantly higher than cells without treatment. We also investigated the effects of these compounds on the expression of apoptosis-related genes BAX, BCL-2, BAD and BIM. Treatment of K562 cells wih compounds 10-14 significantly increased the expression levels of the proapoptotic genes BAX, BAD and BIM, whereas compound 20 increased BAX and BAD.

Human Reproduction, 2021

Study question Could Nrf2 polymorphism (-617C>A; rs6721961) and oxidative stress (OS)-induced ... more Study question Could Nrf2 polymorphism (-617C>A; rs6721961) and oxidative stress (OS)-induced changes of signature seminal plasma (SP) miRNAs related to Nrf2 provide possible biomarkers of male infertility? Summary answer -617C>A SNP is associated with infertility through sperm OS DNA damage and miR-582-5p and miR-20a-5p, differentially represented between spermatozoa of smokers-non-smokers, might regulate Nrf2/ARE axis. What is known already As an extrinsic factor causing OS, smoking decreases male infertility by causing sperm membrane damage and DNA fragmentation. Expression of proteins related to the antioxidant defense system and phase 2 detoxifying enzymes controlled mainly by Nrf2/ARE pathway components is vital in managing OS-induced DNA damage. miRNAs, which multiple of are produced abundantly in male germ cells throughout spermatogenesis, have been detected in SP and contribute to multiple biological processes related to male reproductive events. miRNA-expression alte...

Andrologia, 2016

To evaluate the effects of follicle-stimulating hormone (FSH) treatment on cytokine gene expressi... more To evaluate the effects of follicle-stimulating hormone (FSH) treatment on cytokine gene expression in cultured Sertoli cells from men with nonobstructive azoospermia, a total of 15 azoospermic men diagnosed as obstructive azoospermia (OA) (n = 5) and nonobstructive azoospermia (NOA) (n = 10) were included in the study. NOA patients were split into two further subgroups: nFSH and hFSH serum FSH levels. Expression of cytokine gene panel (88 genes), FSHR and ABP was evaluated by real-time PCR array analysis. FSHR protein level was measured by the Western blot. In primary cultures of Sertoli cells, seven genes were found to be increased and 13 were decreased in NOA group, when compared to OA (p < .05). When rFSH was introduced into the culture media, expression of 12 genes in the NOA group restored a comparable level to those of the control OA group. Sertoli cells in all groups responded rFSH administration with increased expression of ABP. Our results suggest that FSH treatment may have positive effects on Sertoli cells of nonobstructive azoospermic patients via changing the expression levels of certain genes and restoring their levels in normal Sertoli cell population. Some cytokine levels can be considered as a potential candidate for detecting NOA patients. ABP is a good marker for cell viability and functionality in primary Sertoli cell culture.

Andrologia, 2016

The aim of this study was to investigate the relationship of infertility with metalloproteinases ... more The aim of this study was to investigate the relationship of infertility with metalloproteinases ADAMTS1 and ADAMTS5, which are known to be responsible for the degradation of extracellular matrix (ECM) proteins associated with many diseases. ECM is the noncellular component that provides structural and biochemical support to the surrounding cells required for tissue morphogenesis, differentiation and homoeostasis. Sixty infertile individuals and 10 healthy semen donors were included in this study. The infertile individuals were classified as normozoospermia (NS; n = 20), oligozoospermia (OS; n = 20), azoospermia (AS; n = 20) groups. ADAMTS1 and ADAMTS5 protein levels in semen were analysed by Western blot. ADAMTS1 protein level was 3.0-, 3.3and 1.6-fold lower in the OS, AS and NS groups, respectively, than in the control group (P < 0.001). ADAMTS5 protein level was 3.2-, 2.7-and 1.4-fold lower in the OS, AS and NS groups, respectively, than in the control group (P < 0.001). Sperm count and sperm motility showed a negative correlation with the levels of ADAMTS1 and ADAMTS5 protein expression: r = À0.477, r = À0.470; and r = À0.332, r = À0.275 respectively (P < 0.001). In conclusion, ADAMTS1 and ADAMTS5 protein expressions in semen are significantly related with sperm production. It is very important to understand molecular function and organisation of ADAMTSs which will be significant in enlightening the process of spermatogenesis in male infertility.

Genetics and molecular research : GMR, 2007

Telomerase activity is responsible for telomere maintenance and is believed to be crucial in most... more Telomerase activity is responsible for telomere maintenance and is believed to be crucial in most immortal cells and cancer cells; however, its clinicopathological significance in gastric cancer remains to be clarified. The aim of the present study was to assess whether malignant progression of gastric adenocarcinoma correlates with telomerase activity. We also investigated the correlation between telomerase activity and histopathological findings. We examined telomerase activity in tumor specimens and adjacent normal tissues from 43 patients with gastric adenocarcinoma. Telomerase activity was measured quantitatively by the TRAPEZE Gel Based Telomerase Detection Kit. Approximately 98% of the tumor tissues were telomerase positive, but telomerase activity was detected not only in tumor tissues but also in normal gastric mucosa. Although telomerase activity was found to be higher in tumor samples than normal tissue for each subject, we could not find a general cut-off level for telom...

PubMed, Jul 25, 1998

Homozygosity for HLA-DR53 confers increased susceptibility to major forms of leukemia. In childho... more Homozygosity for HLA-DR53 confers increased susceptibility to major forms of leukemia. In childhood leukemia, this influence is male-specific. Two separate studies have shown a male-specific increase in the homozoygosity rate for HLA-DR53 in healthy adults. This finding was attributed to possible preferential transmission of HLA-DR53 towards male offspring. If this is the case, the consequences of such a prenatal event should be evident in the newborn population. The present study investigated HLA-B and -DQA1 genotype frequencies in a sample of 134 newborns (73 boys, 61 girls) in Turkey. Restriction fragment length polymorphism (RFLP) analysis showed a homozygosity rate of 8.2 percent for HLA-DR53. Nine of 11 homozygotes were boys and the sex-specific rates were 12.3 percent vs 3.3 percent in boys and girls, respectively (p = 0.05). The DR53 homozygosity rate in males was higher than the expected rate (p = 0.02). These findings suggested a prenatal mechanism behind the excess of DR53 homozygotes in the male population. To maintain equilibrium, this excess seems to be eliminated postnatally. This model also explains how a deleterious genotype escapes natural selection.

Ankara Üniversitesi Dikimevi Sağlık Hizmetleri Meslek Yüksekokulu dergisi, 2015

Akut Myeloid Lösemi (AML), erken hematopoetik kök hücrelerde bir dizi genetik değişiklik sonucund... more Akut Myeloid Lösemi (AML), erken hematopoetik kök hücrelerde bir dizi genetik değişiklik sonucunda normal büyüme ve farklılaşmanın bozulması, kemik iliği ve periferik kanda çok sayıda anormal olgunlaşmamış myeloid hücrenin birikimi ile karakterize olan bir hastalıktır. Son yıllarda, löseminin oluşum sürecinde DNA metilasyonundaki ve histon modifikasyonlarındaki değişikliklerin etkili olduğu konusunda çalışmalar yapılmış ve AML ve demetile edici ajanlar hematolojik hastalıkların tedavisi için hedef olarak belirlenmiştir. Yüksek doz metilprednizolon yeni tanı almış pediatrik AML hastalarının tedavisinde kısa süreli uygulanmakta ve başarılı sonuçlar alınmaktadır. Sentetik bir glukokortikoid olan metilprednizolonun (MP) yüksek dozda, myeloid lösemi hücrelerinin granülositlere ve makrofajlara farklılaşmasını ve myeloid lösemi hücrelerde apoptozisi indüklediğine dair çalışmalar literatürde bulunmaktadır. Bizim çalışmamızda, AML hücre serisinde metilprednizolonun farklı dozlarda hücreler üzerindeki sitotoksisite düzeylerini saptamak amacıyla MTT yöntemi kullanıldı. MTT testi sonucu canlılığın anlamlı derecede azaldığı dozlarda 24. ve 48. saatlerde apoptozis ve farklılaşma analizleri akım sitometri ile yapıldı. Etken dozun 5x10-3 olarak bulundu ve bu etken dozun uygulandığı HL-60 hücreleri ve kontrol grubu hücrelerinden DNA izolasyonu yapılarak metilasyon analizlerine devam edildi. AML'de sıklıkla metile olduğu bildirilen p15, ER ve anormal ekspresyonu görülen BCL-2 ve CDX2 genlerinin HL-60 AML hücre serisinde steroid tedavisi öncesi ve sonrası metilasyonuna bakılarak, metilprednizolonun etkisini, epigenetik yolaktan gösterip göstermediğini araştırıldı. P15 geni promotoru ve BCL-2 geni promotoru metile bulunmamıştır. ER geni promotoru ve CDX2 geni promotoru ise metile bulunmuştur. MP uygulaması sonrası genlerin metilasyon profillerinde bir değişiklik saptanmamıştır. Çalışmamızda yüksek ve etken dozun hücreleri farklılaşmaya ve apoptozise götürdüğü ancak bunu epigenetik yolak mekanizmalarından biri olan DNA metilasyonu üzerinden yapmadığı saptandı.

International Journal of Hematology and Oncology, Mar 1, 2014

Calcium phosphate is deposited in many diseases, but the molecular basis of mineralization remain... more Calcium phosphate is deposited in many diseases, but the molecular basis of mineralization remains largely unknown. Biomineralizied calcifications that are formed by calcium deposits are also detected in breast mammograms. Some of the detected microcalcifications are thought to be related with malignancy. Taken together, calcifying nanoparticles (CNP) may be thought as a source of malign calcifications in breast cancers. The aim of the study is to research the presence of CNP in breast tumor tissue. With this aim, the presence of CNP was investigated by culturing 16 patients' breast tumor tissue and from 2 pathologic tissues with transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Their growth was monitored by optical density (OD) at a wavelength of 650 nm. CNP couldn't be found in the analysed tissues. The presence of CNP in the breast tumor tissue was researched for the first time. We could not find CNP in the breast tumor tissue, but we think this research will open a new field of study for researchers.

Akut miyeloid losemi (AML), hematopoetik progenitor hucrelerin malign karakter kazanmasi sonucu g... more Akut miyeloid losemi (AML), hematopoetik progenitor hucrelerin malign karakter kazanmasi sonucu gelisen klonal bir hastaliktir. Nukleofosmin (NPM), ribozom biyogenezi, sentrozom duplikasyonu, genomik kararlilik, hucre dongusunun progresyonu ve apoptozisin de dahil oldugu bircok hucresel surecte onemli roller ustlenen nukleolar bir fosfoproteindir. NPM geninin (NPM1) 12. ekzonunda meydana gelen somatik mutasyonlar, AML vakalarinda en sik gorulen genetik anomalilerdir. Tum AML vakalarinin yaklasik %35’inde NPM1 gen mutasyonlarina rastlanirken, soz konusu mutasyonlari tasiyan AML vakalarinin %60’indan fazlasi normal karyotipe sahiptir. NPM1 mutasyonlarini tasiyan AML vakalari, karakteristik klinik ve prognostik ozelliklere sahiptirler. Bu calismada, NPM1 gen mutasyon sikliklari Turk AML hastalarinda arastirilmistir. AML tanisi almis 44 hasta ve 12 saglikli kontrol calismaya dahil edilmistir. NPM1 mutasyonlari nested PCR yontemiyle, genotipler ise poliakrilamid jel elektroforezi ve jel goruntuleme sistemi kullanilarak belirlenmistir. NPM1 gen mutasyonlari 44 hastanin 8’inde (%18,18) saptanirken, saglikli kontrollerde mutasyon saptanmamistir. NPM1 gen mutasyonlari, onemli olcude normal karyotipli AML hastalari ile iliskilendirilmistir. Ayrica soz konusu mutasyonlar ileri yas, yuksek beyaz kure sayisi, primer AML, yuksek kemik iligi blast yuzdesi, FAB alttipleri M1/M5 ve CD34’un negatif ekspresyonu ile iliskilendirilmistir. Fakat bu sonuclar istatistiksel acidan anlamli bulunmamistir. Bu calismadan elde edilen sonuclarin, AML’li hastalarin tedavilerinin yonlendirilmesine ve hastaligin siniflandirilmasina katki saglayacagi dusunulmektedir.AbstractAcute myeloid leukemia (AML) is a clonal disorder that results from gain of malignant characteristics of hematopoetic progenitor cells. Nucleophosmin is a nucleolar phosphoprotein that plays key roles in several cellular processes including ribosome biogenesis, centrosome duplication, genomic stability, cell cycle progression and apoptosis. Somatic mutations occurring in exon 12 of the NPM gene (NPM1) are the most common genetic abnormalities seen in AML cases. NPM1 gene mutations are found in approximately 35% of all AML cases and up to 60% of AML cases carrying these mutations have normal karyotype. AML cases carrying NPM1 mutations have characteristic clinical and prognostic features. In this study, NPM1 gene mutation frequencies are assessed in Turkish AML patients. 44 AML diagnosed patients and 12 healthy controls were admitted to the study. NPM1 mutations were determined by nested PCR assay, genotypes were determined by using polyacrylamide gel electrophoresis and image analyzer system. NPM1 gene mutations were detected in 8 of the 44 (%18,18) patients but not in healthy controls. NPM1 gene mutations were significantly associated with AML patients with normal karyotype. Additionally these mutations were associated with old age, high white blood cell count, primer AML, high bone marrow blast percentage, FAB subtypes M1/M5 and negative expression of CD34. But these results were not found statistically significant. It is thought that the results obtained from this study contribute to routing of the treatment of patients with AML and classification of the disesia.

Naunyn-Schmiedeberg's archives of pharmacology, Jun 25, 2024

Türkiye fiziksel tıp ve rehabilitasyon dergisi, 2016

The Turkish Journal Of Occupational / Environmental Medicine and Safety, Feb 16, 2017

Molecular Biology Reports, Dec 14, 2022

Zeitschrift für Naturforschung C, Mar 1, 2015

Ankara Üniversitesi Eczacılık Fakültesi dergisi, Sep 27, 2022

Archives of Pharmacal Research, Jul 18, 2014

Human Reproduction, 2021

Andrologia, 2016

Genetics and molecular research : GMR, 2007

PubMed, Jul 25, 1998

Ankara Üniversitesi Dikimevi Sağlık Hizmetleri Meslek Yüksekokulu dergisi, 2015

International Journal of Hematology and Oncology, Mar 1, 2014