Browsing by Author "Tobu, M"

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    Augmentation of methylprednisolone-induced differentiation of myeloid leukemia cells by serine threonine protein phosphatase inhibitors
    Uzunoglu, S; Uslu, R; Tobu, M; Saydam, G; Terzioglu, E; Buyukkececi, F; Omay, SB
    To elucidate the roles of serine/threonine protein phosphatases type 1 (PP1) and type 2A (PP2A) in methylprednisolone-induced differentiation of HL60 cells into granulocytes and K562 cells into monocytes, we examined the effect of serine/threonine protein phosphatase inhibitors, okadaic acid and Gal-A on the proliferation/ differentiation of HL60 and K562 cells. Okadaic acid and Gal-A augmented methylprednisolone induced granulocytic differentiation and cell death of HL60 cells and monocytic differentiation and cell death of K562 cells in different dose ranges, respectively. These data suggest an important role of PP1 and PP2A in the mechanism leading to differentiation of leukemic cells. (C) 1999 Elsevier Science Ltd. AU rights reserved.
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    Up-regulation of serine/threonine protein phosphatase type 2A regulatory subunits during methylprednisolone-induced differentiation of leukaemic HL-60 cells
    Aydin, HH; Selvi, N; Saydam, G; Tobu, M; Uzunoglu, S; Uslu, R; Buyukkececi, F; Omay, SB
    Serine/threonine protein phosphatase 2A (PP2A) may play a role in leukaemic cell differentiation of the HL 60 myeloid leukaemic cell-line after methylprednisolone induction. We have investigated the specific enzyme activity and expression of catalytic and regulatory subunits of PP2A. The resulting specific enzyme activity and immunoblots showed an increase in enzyme activity and the expression of regulatory subunits after methylprednisolone treatment. There was no change in the expression of PP2A catalytic subunits. It is suggested that the effect of methylprednisolone on leukaemic differentiation may be the result of PP2A upregulation.
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    Identification of the molecular etiology in rare congenital hemolytic anemias using next-generation sequencing with exome-based copy number variant analysis
    Isik, E; Aydinok, Y; Albayrak, C; Durmus, B; Karakas, Z; Orhan, MF; Sarper, N; Aydin, S; Unal, S; Oymak, Y; Karadas, N; Turedi, A; Albayrak, D; Tayfun, F; Tugcu, D; Karaman, S; Tobu, M; Unal, E; Ozcan, A; Unal, S; Aksu, T; Unuvar, A; Bilici, M; Azik, F; Ay, Y; Gelen, SA; Zengin, E; Albudak, E; Eker, I; Karakaya, T; Cogulu, O; Ozkinay, F; Atik, T
    ObjectivesIn congenital hemolytic anemias (CHA), it is not always possible to determine the specific diagnosis by evaluating clinical findings and conventional laboratory tests. The aim of this study is to evaluate the utility of next-generation sequencing (NGS) and clinical-exome-based copy number variant (CNV) analysis in patients with CHA.MethodsOne hundred and forty-three CHA cases from 115 unrelated families referred for molecular analysis were enrolled in the study. Molecular analysis was performed using two different clinical exome panels in 130 patients, and whole-exome sequencing in nine patients. Exome-based CNV calling was incorporated into the traditional single-nucleotide variant and small insertion/deletion analysis pipeline for NGS data in 92 cases. In four patients from the same family, the PK Gypsy variant was investigated using long-range polymerase chain reaction.ResultsMolecular diagnosis was established in 86% of the study group. The most frequently mutated genes were SPTB (31.7%) and PKLR (28.5%). CNV analysis of 92 cases revealed that three patients had different sizes of large deletions in the SPTB and six patients had a deletion in the PKLR.ConclusionsIn this study, NGS provided a high molecular diagnostic rate in cases with rare CHA. Analysis of the CNVs contributed to the diagnostic success.