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  • Küçük Resim
    Öğe
    Effects Of Rituximab On Jak-Stat And Nf-?b Signaling Pathways İn Acute Lymphoblastic Leukemia And Chronic Lymphocytic Leukemia
    (Türk Biyokimya Derneği, 2019) Dalmızrak, Ayşegül; Günel, Nur Selvi; Kaymaz, Burçin Tezcanlı; Fahri, Şahin; Saydam, Güray; Kosova, Buket
    Objectives: Rituximab is a monoclonal antibody that targets the B-lymphocyte surface antigen CD20. It is used in the treatment of some diseases including B-cell chronic lymphocytic leukemia (B-CLL). There are a lot of data regarding effect of Rituximab on lymphoma cells. But, there is no satisfactory information about the effect of Rituximab on the signaling pathways in leukemia cells. In this study, it was aimed to understand the effect of Rituximab on JAK-STAT and NF-?B signaling pathways in B-cellacute lymphoblastic leukemia (B-ALL) and B-CLL. Material and methods: Apoptotic effect of Rituximab in the TANOUE (B-ALL) and EHEB (B-CLL) cell lines were evaluated by using the Annexin V method. mRNA expression levels of STAT3 and RelA were analysed by quantitative RT-PCR (Q-PCR). Alterations in STAT3 and RelA protein expressions were detected by using a chromogenic alkaline phosphatase assay after Western Blotting. Results: Rituximab had no apoptotic effect on both cell lines. Complement-mediated cytotoxicity was only detected in EHEB cells. mRNA and protein expressions of STAT3 and RelA genes were decreased following Rituximab treatment. Conclusion: Our preliminary results suggest that the use of Rituximab might be effective in B-ALL though both signaling pathways.
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    Thiopurine-S-Methyltransferase Gene Polymorphism and Drug-related Toxicity in Children Treated for Acute Leukemia and Non-Hodgkin’s Lymphoma
    (Galenos Publishing House, 2022) Aktan, Çağdaş; Ataseven, Eda; Kosova, Buket; Kurugöl, Zafer; Kantar, Mehmet
    Aim: Thiopurine S-methyltransferase (TPMT) is an essential enzyme in the metabolism of thiopurine drugs, and its activity may change due to different polymorphisms in the TPMT gene. The TPMT gene has different genetic polymorphisms in different ethnic groups. This study aimed to determine the frequency of TPMT polymorphisms in children with acute leukemia/non-Hodgkin lymphoma (AL/NHL) and healthy children and to evaluate their association with severe toxicities in the study population. Materials and Methods: Sixty-seven pediatric AL/NHL patients and 84 healthy children were evaluated. Genotyping for the TPMT*2, TPMT*3A, TPMT*3B, TPMT*3C, TPMT*4, TPMT*5, TPMT*6, and TPMT*7 alleles were performed by the real-time polymerase chain reaction technique. The number of grade 3 or higher hematologic and hepatic toxicities were recorded from the patient charts. Results: In the AL/NHL patients, we found that the patients had generally wild-type TPMT*1 allele in 80.6%, whereas TPMT*2 (238G>C) was seen in 1.5%, TPMT*3A (c.460G>A and c.719A>G) in 0%, and TPMT*3B polymorphisms (460G>A) in 17.9%. We found wild-type TPMT*1 allele in 98.8% and TPMT*3B polymorphisms (460G>A) in 1.2% of the healthy volunteers. Grade ?3 myelosuppression developed in 22/54 patients with the wild type allele, and it developed in 5/12 patients with TPMT*3B allele. Six (8.9%) patients had grade ?3 aspartate aminotransferase elevations, 17 (25%) patients had grade ?3 alanine transaminase elevations (1-5 times), and 42 patients had (62.6%) grade ?3 total bilirubin elevations. Conclusion: TPMT*3B polymorphism was the most common allele detected in our study group. This allele frequency is very high in comparison to other studies from our country and it was over-represented in comparison to the healthy volunteers. We did not find any relationship between severe hematologic/hepatic toxicities and TPMT gene polymorphisms.