Fahri Şahin

Caffeic acid phenethyl ester triggers apoptosis through induction of loss of mitochondrial membrane potential in CCRF-CEM cells

PurposeCAPE (caffeic acid phenethyl ester) is one of the most valuable and investigated component of propolis which is composed by honeybees. In the current study, we aimed at examining apoptotic effects of CAPE on CCRF-CEM leukemic cells and at determining the roles of mitochondrial membrane potential (MMP) in cell death.MethodsTrypan blue and XTT methods were used to evaluate the cytotoxicity. Apoptosis was examined by ELISA-based oligonucleotide and acridine orange/ethidium bromide dye techniques. Loss of mitochondrial membrane potential was evaluated using JC-1 dye by flow cytometric analysis and under fluorescent microscope.ResultsWe detected the time- and dose-dependent increases in cytotoxic effect of CAPE on CCRF-CEM cells. ELISA and acridine orange/ethidium bromide results showed that apoptotic cell population increased significantly in CCRF-CEM cells exposed to increasing concentrations of CAPE. On the other hand, there was significant loss of MMP determined in response to CAPE in CCRF-CEM cells.ConclusionThis in vitro data by being supported with clinical data may open the way of the potential use of CAPE for the treatment of leukemia.

Quality of Life and Supportive Care in Multiple Myeloma

Multiple myeloma is the second most common haematological malignancy. Novel therapies have led to improvement in survival. Current myeloma management is matching the progress made in improved survival through disease control while optimising quality of life with effective supportive care. Supportive treatment is an essential part of the therapeutic management of myeloma patients because it is directed towards improving the patient’s quality of life and also can improve survival. The aim of this review is to highlight the relationship among life of quality, supportive care, and improvement in survival. Conflict of interest:None declared.

Methylprednisolone induces apoptosis by interacting with the JAK/STAT pathway in HL-60 and K-562 leukemic cells

Abstract Objective To determine the gene expression profiles of the JAK/STAT pathway members STAT3, STAT5A, STAT5B at both mRNA and protein levels in HL-60 and K-562 leukemia cells that were undergoing apoptosis following high-dose methylprednisolone (MP) treatment. Methods HL-60 cells were treated with 0.1 mM MP and K-562 cells were treated with 0.4 mM MP according to their IC50 values. STAT3, STAT5A, and STAT5B mRNA relative expression levels were determined by qRT-PCR whereas the protein levels were detected via western-blot analysis and apoptosis was evaluated by Annexin V method. Results A significant decrease was seen in STAT5A mRNA relative expression level at 48 hours of MP treatment (P < 0.05) both in HL-60 and K-562 cells. Other STATs showed a lower downregulation in their relative expressions at 48 hours at mRNA level for both of the cell lines. STAT proteins showed no expression change in K-562 cells in time course experiments but while STAT5A expression was downregulated; STAT5B showed an increase at 96 hours in HL-60 cells. Apoptosis was triggered by high-dose MP treatment that was evaluated by fluorescent microscopy. Conclusion The JAK/STAT pathway components may play an important role in the apoptosis mechanism of leukemic cells under MP treatment in HL-60 and K-562 cells. Other pathways may also be involved with a post-translational modification seen in the HL-60 cell line, with both upregulation and downregulation of protein expression levels of STAT5B and STAT5A, respectively.

Turkish Chronic Myeloid Leukemia Study: Retrospective Sectional Analysis of CML Patients

Objective: here have been tremendous changes in treatment and follow-up of patients with chronic myeloid leukemia (CML) in the last decade. Especially, regular publication and updating of NCCN and ELN guidelines have provided enermous rationale and base for close monitorization of patients with CML. But, it is stil needed to have registry results retrospectively to evaluate daily CML practices. Materials and Methods: In this article, we have evaluated 1133 patients’ results with CML in terms of demographical features, disease status, response, resistance and use of second-generation TKIs. Results: The response rate has been found relatively high in comparison with previously published articles, and we detected that there was a lack of appropriate and adequate molecular response assessment. Conclusion: We concluded that we need to improve registry systems and increase the availability of molecular response assessment to provide high-quality patient care. Conflict of interest:None declared.

Bortezomib induces apoptosis by interacting with JAK/STAT pathway in K562 leukemic cells

In the current study, we aimed to identify the cytotoxic and apoptotic effects of bortezomib (BOR) on human K562 chronic myelogenous leukemia cells and to evaluate the potential roles of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway members STAT3, STAT5, and JAK2 on BOR-induced cell death of leukemic cells. Cell viability was assessed via trypan blue dye exclusion test, and cytotoxicity of the BOR-treated cells was conducted by 2,3-bis(2-methoxy-4-nitro-5-sulphophenyl)-2H-tetrazolium-5-carboxanilide inner salt (XTT) assay. The relative messenger RNA (mRNA) expression levels of STAT3, STAT5A, STAT5B, and JAK2 were analyzed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). On the other hand, their protein expression levels were detected by western blot method. The obtained results indicated that BOR treatment reduced cell viability and induced leukemic cell apoptosis in a dose- and time-dependent manner as compared to untreated control cells. While mRNA expression levels of STAT5A, STAT5B, and STAT3 were significantly reduced following BOR treatment when compared to untreated controls, it had no effect upon JAK2 mRNA expression. As for protein levels, STAT expressions were downregulated after BOR treatment especially at 72nd and 96th hours. Our results pointed out that BOR treatment had a significant potential of being an anticancer agent for chronic myelogenous leukemia therapy, and this effect could be due to the expressional downregulations of JAK/STAT pathway members.

The Role of Azacitidine in the Treatment of Elderly Patients with Acute Myeloid Leukemia: Results of a Retrospective Multicenter Study

Objective: In this study, we aimed to investigate the efficacy and safety of azacitidine (AZA) in elderly patients with acute myeloid leukemia (AML), including patients with >30% bone marrow (BM) blasts. Materials and Methods: In this retrospective multicenter study, 130 patients of ≥60 years o ld who were ineligible for intensive chemotherapy or had progressed despite conventional treatment were included. Results: The median age was 73 years and 61.5% of patients had >30% BM blasts. Patients received AZA for a median of four cycles (range: 1-21). Initial overall response [including complete remission (CR)/CR with incomplete recovery/partial remission] was 36.2%. Hematologic improvement (HI) of any kind was documented in 37.7% of all patients. HI was also documented in 27.1% of patients who were unresponsive to treatment. Median overall survival (OS) was 18 months for responders and 12 months for nonresponders (p=0.005). In the unresponsive patient group, any HI improved OS compared to patients without any HI (median OS was 14 months versus 10 months, p=0.068). Eastern Cooperative Oncology Group performance status of <2, increasing number of AZA cycles (≥5 courses), and any HI predicted better OS. Age, AML type, and BM blast percentage had no impact. Conclusion: We conclude that AZA is effective and well tolerated in elderly comorbid AML patients, irrespective of BM blast count, and HI should be considered a sufficient response to continue treatment with AZA.

Investigating the Role of JAK/STAT Pathway on Dasatinib-Induced Apoptosis for CML Cell Model K562

We aimed to evaluate the cytotoxic and apoptotic effects of dasatinib (BMS-354825) on K562 chronic myeloid leukemia (CML) cells and to examine the roles of STAT genes on dasatinib-induced apoptosis. The results showed that dasatinib decreased proliferation and induced apoptosis in K562 cells in a dose- and time-dependent manner. mRNA and protein levels of STAT5A and STAT5B genes were significantly reduced in dasatinib-treated K562 cells. These data indicated that STAT inhibition by dasatinib might be therapeutic in JAK/STAT pathway-associated malignancies after confirmation with clinical studies.

Epidemiology and analysis of invasive fungal infections in patients withhematological malignancies: a single-center real-life experience

Background/aim: Invasive fungal infection (IFI) causes morbidity and mortality among patients with hematological malignancies. We evaluated the incidence and treatment characteristics of IFIs between October 2012 and December 2013. Materials and methods: Patients who received chemotherapy or stem cell transplantation were retrospectively evaluated. Fungal infections were classified according to EORTC criteria.Results: Prophylaxis and antifungal therapy were given in 30.5% and 23.6% of 522 chemotherapy courses, respectively. The incidence of proven/probable IFI was 6.7%. The incidence of IFI among patients who received prophylaxis was significantly higher than among those who did not receive it (11.3% vs. 4.6%, P = 0.005). There was no significant difference between patients who received mold-active and no mold-active prophylaxis (P = 0.098). The most common single agent therapy and causative pathogen was liposomal amphotericin B (57.1%) and Aspergillus (n = 5), respectively. IFI-attributable mortality rate was 14.2% in 6 weeks.Conclusion: The IFI incidence and mortality rate were similar to that reported in the literature. The IFI rate was higher in the group using prophylaxis, as this is a high-risk group. Although the IFI rate was not significantly different between groups using prophylaxis, patients should be followed closely for the effective use of posaconazole prophylaxis.

Eltrombopag for the Treatment of Immune Thrombocytopenia: The Aegean Region of Turkey Experience.

Objective: Immune thrombocytopenia (ITP) is an immune-mediated disease characterized by transient or persistent decrease of the platelet count to less than 100x109/L. Although it is included in a benign disease group, bleeding complications may be mortal. With a better understanding of the pathophysiology of the disease, thrombopoietin receptor agonists, which came into use in recent years, seem to be an effective option in the treatment of resistant cases. This study aimed to retrospectively assess the efficacy, long-term safety, and tolerability of eltrombopag in Turkish patients with chronic ITP in the Aegean region of Turkey. Materials and Methods: Retrospective data of 40 patients with refractory ITP who were treated with eltrombopag in the Aegean region were examined and evaluated. Results: The total rate of response was 87%, and the median duration of response defined as the number of the platelets being over 50x109/L was 19.5 (interquartile range: 5-60) days. In one patient, venous sinus thrombosis was observed with no other additional risk factors due to or related to thrombosis. Another patient with complete response and irregular follow-up for 12 months was lost due to sudden death as the result of probable acute myocardial infarction. Conclusion: Although the responses to eltrombopag were satisfactory, patients need to be monitored closely for overshooting platelet counts as well as thromboembolic events.

Ocular Adnexal Lymphomas: Single-Center Experience

Ocular adnexal lymphoma (OAL) is a rare manifestation of non-Hodgkin lymphoma consisting of the tissues and structures surrounding the eye that include the conjunctiva, eyelids, lacrimal gland, and orbital soft tissues. OAL comprise 1% to 2% of all non-Hodgkin lymphomas and about 8% of the extranodal lymphomas; however, the incidence of OAL has increased by approximately 6% annually in last 2 decades, and OAL now represents the majority of orbital malignancies. There are no uniform treatment guidelines for OAL. Because of high local and extraorbital recurrence rates, appropriate local, systemic, or combined treatment must be applied.