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Copyright of Turkish Journal of Intensive Care is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma (NHL) subtype characterized by overexpression of CCND1 and SOX11 genes. It is generally associated with clinically poor outcomes despite recent improvements in therapeutic approaches. The genes associated with the development and prognosis of MCL are still largely unknown. Through whole transcriptome sequencing (WTS), we identified mRNAs, lncRNAs, and alternative transcripts differentially expressed in MCL cases compared with reactive tonsil B-cell subsets. CCND1, VCAM1, and VWF mRNAs, as well as MIR100HG and ROR1-AS1 lncRNAs, were among the top 10 most significantly overexpressed, oncogenesis-related transcripts. Survival analyses with each of the top upregulated transcripts showed that MCL cases with high expression of VWF mRNA and low expression of FTX lncRNA were associated with poor overall survival. Similarly, high expression of MSTRG.153013.3, an overexpressed alternative transcript, was associated with shortened MCL survival. Known tumor suppressor candidates (e.g., PI3KIP1, UBXN) were significantly downregulated in MCL cases. Top differentially expressed protein-coding genes were enriched in signaling pathways related to invasion and metastasis. Survival analyses based on the abundance of tumor-infiltrating immunocytes estimated with CIBERSORTx showed that high ratios of CD8+ T-cells or resting NK cells and low ratios of eosinophils are associated with poor overall survival in diagnostic MCL cases. Integrative analysis of tumor-infiltrating CD8+ T-cell abundance and overexpressed oncogene candidates showed that MCL cases with high ratio CD8+ T-cells and low expression of FTX or PCA3 can potentially predict high-risk MCL patients. WTS results were cross-validated with qRT-PCR of selected transcripts as well as linear correlation analyses. In conclusion, expression levels of oncogenesis-associated transcripts and/or the ratios of microenvironmental immunocytes in MCL tumors may be used to improve prognostication, thereby leading to better patient management and outcomes. [ABSTRACT FROM AUTHOR]

Follicular lymphoma (FL) is the second most frequent non-Hodgkin lymphoma accounting for 10-20% of all lymphomas in western countries. As a clinically heterogeneous cancer, FL occasionally undergoes histological transformation to more aggressive B cell lymphoma types that are associated with poor prognosis. Here we evaluated the potential of circulating cell-free DNA (cfDNA) to improve the diagnosis and prognosis of follicular lymphoma patients. Twenty well-characterized FL cases (13 symptomatic and 7 asymptomatic) were prospectively included in this study. Plasma cfDNA, formalin-fixed paraffin-embedded (FFPE) tumor tissue DNA, and patient-matched granulocyte genomic DNA samples were obtained from 20 treatment-naive FL cases. Ultra-deep targeted next-generation sequencing was performed with these DNA samples by using a custom-designed platform including exons and exon-intron boundaries of 110 FL related genes. Using a strict computational bioinformatics pipeline, we identified 91 somatic variants in 31 genes in treatment-naive FL cases. Selected variants were cross-validated by using PCR-Sanger sequencing. We observed higher concentrations of cfDNA and a higher overlap of somatic variants present both in cfDNA and tumor tissue DNA in symptomatic FL cases compared to asymptomatic ones. Variants known to be associated with FL pathogenesis such as STAT6 p.D419 or EZH2 p.Y646 were observed in patient-matched cfDNA and tumor tissue samples. Consistent with previous observations, high Ki-67 staining, elevated LDH levels, FDG PET/CT positivity were associated with poor survival. High plasma cfDNA concentrations or the presence of BCL2 mutations in cfDNA showed significant association with poor survival in treatment-naive patients. BCL2 mutation evaluations in cfDNA improved the prognostic utility of previously established variables. In addition, we observed that a FL patient who had progressive disease contained histological transformation-associated gene (i.e. B2M and BTG1) mutations only in cfDNA. Pre-treatment concentrations and genotype of plasma cfDNA may be used as a liquid biopsy to improve diagnosis, risk stratification, and prediction of histological transformation. Targeted therapies related to oncogenic mutations may be applied based on cfDNA genotyping results. However, the results of this study need to be validated in a larger cohort of FL patients as the analyses conducted in this study have an exploratory nature. [ABSTRACT FROM AUTHOR]

Copyright of Turkish Journal of Hematology is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Turkish Journal of Hematology is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL). The treatment of older NHL patients has always been a struggle; however, treatment statistics have begun showing favorable results similar to those of younger DLBCL patients thanks to newer treatment protocols. Here, we analyze the progress of our own elderly DLBCL patients who were followed between 2000 and 2016 in our center. Materials and Methods: Eighty-seven DLBCL patients, who were diagnosed and treated in the Dokuz Eylül University Department of Hematology between 2000 and 2016, were included in this study. Median age was 72 (65-89) years and 13 (14.9%) patients were older than 80 years. Results: Median follow-up time was 19 months and 45 patients (51.7%) died during the follow-up period. Median overall survival (OS) was 55 months and median progression-free survival was calculated as 27 months. Sixty-three patients (72.4%) received standard R-CHOP therapy. Complete response was seen in 46 (52.9%) patients. The median survival time for patients who had complete response was 136 months (p<0.001); however, OS was not statistically different between older (>80 years) and younger patients (p=0.236). Conclusion: According to our findings, we think that being able to complete standard R-CHOP therapy is vital for the survival rate of elderly DLBCL patients. [ABSTRACT FROM AUTHOR]

Dyskeratosis congenita (DC) is a rare inherited syndrome characterized by classical mucocutaneous features and the presence of other clinical features including bone marrow failure, pulmonary fibrosis, liver cirrhosis, and a predisposition to cancer. The symptoms develop at various ages and may manifest over time. Gene mutations associated with DC, such as DC1, TERC, TERT, TINF2, NHP2, NOP10, ACD, CTC1, NAF1, PARN, POT1, RTEL1, STN1, and WRAP53, have been identified in about 70% of patients. Since the number of patients with DC is small and the effect of genetic pathogenic variant may affect the phenotype, we wanted to present the clinical features and course of illness in a patient with NHP2 gene mutation (compound heterozygote for the NHP2 mutations c.376G>A/c.460T>A; amino acid substitutions: p.Val126Met and p.X154Arg) that occurred as a compound heterozygous state. [ABSTRACT FROM AUTHOR]

Copyright of Turkish Journal of Hematology is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: There have been concerns about the possible prothrombotic effects of nilotinib, especially in patients having cardiovascular risk factors. The potential mechanism behind the increased risk of thromboembolic events is still not clear. Objectives: In this study, we aimed to evaluate possible harmful effects of nilotinib on endothelial cells. To this aim, we examined proliferative capacity and secretory functions of healthy human carotid artery endothelial cells (HCtAECs) in response to nilotinib. Methods: 3-(4,5-Dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation method was used to determine antiproliferative effects of nilotinib on HCtAECs. The HCtAECs were incubated with 5, 10, and 100 nmol/L doses of nilotinib for 72 hours. Then, in order to assess the endothelial function, levels of nitric oxide (NO), von Willebrand factor (vWF), tissue plasminogen activator, plasminogen activator inhibitor 1 (PAI-1), and endothelin 1 (ET-1) were evaluated using enzyme-linked immunosorbent assay from tissue culture supernatants. Results: There were slight but statistically significant decreases in cell proliferation in response to nilotinib. Nilotinib increased the secretion of t-PA, PAI-1, and vWF in a dose-dependent manner when compared with the untreated control group. The ET-1 secretion was lower in 5 nmol/L and higher in 10 and 100 nmol/L nilotinib-treated cells as compared to untreated cells. Regarding NO secretion, lower levels were observed in 5 and 10 nmol/L, and higher levels were detected in 100 nmol/L nilotinib-treated cells as compared to untreated control group cells. Conclusion: Considering the results obtained in our study, nilotinib does not affect the functions of endothelial cells either in a prothrombotic or an antithrombotic fashion, despite a dose-dependent decline in cell viability. [ABSTRACT FROM AUTHOR]

Copyright of Turkish Journal of Hematology is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Bilateral non-granulomatous anterior uveitis with left vitritis and macular edema were detected in a 19-year-old woman presenting with blurred vision in her left eye. Light microscopic study of the pathologic mediastinal lymph node that was detected via contrast computed tomography imaging during etiologic study revealed nodular sclerosing and mixed cellularity Hodgkin's lymphoma (HL). Ocular findings completely resolved with adriablastin, bleomycin, vinblastine, dacarbazine chemotherapy treatment. Herein, it is emphasized that HL should be remembered as one of the differential diagnoses in patients with ocular inflammatory pathologies such as uveitis and vasculitis. The ocular findings of HL are discussed. [ABSTRACT FROM AUTHOR]

Objective: Diffuse large B cell lymphoma (DLBCL) is the most common type of adult lymphoma. No certain histopathological parameter was found, except proliferation index, for predicting prognosis. In hematological malignancies, the prognostic effect of Nm23 expression, which shows metastatic potential in solid tumors, has been researched by a few studies. Loss of p27, a negative regulator of the cell cycle, indicates aggressiveness; however, some studies showed that high expression is relevant to poor prognosis. Here, we aimed to investigate whether they can be used as prognostic markers in DLBCLs. Materials and Methods: Forty-two cases were included in the study. Demographic data were collected from hospital records. Manual immunohistochemical staining procedure was performed on one paraffin block of every case. Intensity and percentage of staining were grouped as positive and negative. Results: From 25 males and 17 female patients with a mean age of 62.9, 28 cases (66.7%) were Nm23-positive, and 13 (30.9%) were p27-positive. International Prognostic Index (IPI) score was relevant to prognosis. No significant relationship was found between prognosis and the expression of these two markers. Conclusion: Advanced age, high IPI score, and high serum lactate dehydrogenase (LDH) level were considered poor prognostic factors in DLBCLs. Larger series are needed for using Nm23 and p27 in predicting prognosis because of different results in the literature. [ABSTRACT FROM AUTHOR]

Aim: We aimed to investigate the effects of interim positron emission tomography (PET)/ computerized tomography (CT) adaptive treatment strategies on disease prognosis. Method: The study included 90 Diffuse Large B Cell Lymphoma (DLBCL) and 67 Hodgkin Lymphoma (HL) patients. The pre-treatment and interim PET/CT images were evaluated by two nuclear medicine doctors as a blind experiment. Only PET/CT was performed in 104 patients, both PET/CT and CECT in 17 patients, only contrast-enhanced CT in 36 patients. Evaluation of treatment response was performed according to Deauville 5P criteria. The first and interim CT scans of 53 patients with CT at the time of diagnosis were blinded by two radiologists. A total of five target lesions were selected for each patient, two for spleen and liver. Two-dimensional measurements of the lesions were performed pre-treatment and interim CT. Interim responses and end-of-treatment responses of the patients were compared using SPSS 22.0 statistical analysis program. Results: Interim PET/CT PPV was 36% for HL, 61.9% for DLBCL; NPV was 95.4% for HL and 93.1 for DLBCL. PPV and NPV were calculated separately for each risk group of HL and DLBCL. The 7-year progression-free survival rate was 54% for PET + patients and 83% for PET-patients in HL, and was 20% for PET+ and 79% for PET- DLBCL patients. CT response was negative despite PET positivity for 2 of 8 patients who were evaluated with interim PET/CT and contrast-enhanced CT in the DLBCL group. CT response was positive despite PET negativity for 3 of 9 patients who were evaluated with interim PET/CT and contrast-enhanced CT in the HL group. In the group of 157 patients, interim Lugano PET/CT-related response and interim Lugano and RECIST 1.1 CT-related responses were found to be negligible in the kappa analysis. PET/ CT-related response was more compatible with treatment response than CTrelated response. Conclusion: PET/CT prevented some patients to receive unnecessary and intensive treatments and some patients to have inadequate treatment and improved the evaluation of lymphoma treatment response significantly. The use of the Deauville criteria standardized the comparability between the images. PET/CT has high NPV and low-medium PPV in both HL/DLBCL groups and in individual risk groups. PET negativity is a prognostic indicator with a high specificity for progression-free survival. Treatment intensification based only on interim PET positivity may cause patients to be exposed to unnecessary drug toxicity. [ABSTRACT FROM AUTHOR]

It has been shown that imatinib mesylate, a drug used in the treatment of chronic myelogenous leukemia, inhibits the effect of stem cell factor, which has a central role in erythropoiesis. In some polycythemia vera (PV) patients, it has inhibited autonomous erythroid colony growth in vitro and decreased the need for phlebotomy. In this study we have investigated the effect of insulin like growth factor (IGF)-I, stem cell factor (SCF) and erythropoietin (Epo) with interleukin (IL)-3, granulocyte macrophage-colony stimulating factor (GM-CSF) and granulocyte-colony stimulating factor (G-CSF) in the presence of imatinib mesylate on the erythroid progenitors derived from peripheral blood mononuclear cells of three patients with PV and four healthy controls in semisolid medium. Erythroid colony formation from hematopoietic progenitors obtained from healthy controls was observed only in the presence of all cytokines. However, the number of erythroid colonies could not reach that of patients with PV. Inhibition of imatinib mesylate on erythroid colony growth was evident. Hematopoietic progenitors of patients with PV displayed two types of colony formation: the first type was exogenous cytokine-independent and was hypersensitive to current cytokines, and the second displayed hypersensitivity to current exogenous cytokines, but was exogenous cytokine-dependent. For both types, the inhibitory effect of imatinib mesylate was striking in the presence of all cytokines including IL-3, GM-CSF and Epo. There is no direct evidence yet that imatinib mesylate could inhibit the effect of IL-3, G-CSF, GM-CSF, Epo and IGF-I on erythropoiesis. Considering former studies together with results of this study, it can be argued that imatinib mesylate is effective in PV on the intersecting signal transduction mechanisms in which stem cell factor and its receptor may have a part.

Background: The clinical course of patients with inflammatory bowel disease (IBD) is frequently complicated by thromboembolic events and may involve the arterial and venous systems. Although not uniformly documented, several studies document substantial alterations in markers of coagulation and fibrinolysis in patients with IBD., Methods: 45 patients with IBD (31 UC,14 CD) were included in the study. Age and sex matched 16 volunteers were used as a control group. TAFI antigen was determined using an ELISA kit VisuLiseTM for quantitative measurement., Results: Inflammatory parameters such as white blood cell, platelet levels, erythrocyte sedimentation rate, C-reactive protein were found to be significantly higher in active disease group compared to inactive patients. Coagulation parameters of prothrombin time, activated partial thromboplastin time and d-dimer levels showed no significant difference between active and inactive IBD. Fibrinogen levels were significantly higher in clinically active IBD patients. Plasma TAFI levels demonstrated no significant difference between active and control, inactive and control as well as active and inactive groups. We observed no significant changes in levels of β-TG and PF-4 between active and inactive disease group., Conclusions: We studied plasma TAFI levels in IBD. In conclusion, plasma TAFI levels does not appear to represent to be a marker of activation in IBD in contrast to literature. So further studies covering more patients with different clinic and disease activity status might improve the perspective on this issue.

t(1;3)(p36;p21) is a recurrent reciprocal translocation found in a subset of myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) characterized by trilineage dysplasia, especially dysmegakaryopoiesis and poor prognosis. In the literature, some authors have suggested that this recurrent translocation is closely associated with prior chemotherapy including alkylating agents in various hematologic malignancies. We identified a recurring translocation, t(1;3)(p36;p21), in our patient with MDS/AML(M2), although she had not been given any kind of treatment previously.