فهرست مطالب

  • Volume:14 Issue: 1, 2020
  • تاریخ انتشار: 1398/10/11
  • تعداد عناوین: 8
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  • Hitoshi Yoshida*, Midori Koike, Yuma Tada, Keiichi Nakata, Akihisa Hino, Shigeo Fuji, Hiroaki Masaie, Chihiro Oka, Akemi Higeno, Atushi Idota, Tomoyuki Yamasaki, Jun Ishikawa Pages 1-10
    Background

    Advances of allogeneic hematopoietic cell transplantation (allo-HCT) have brought long-term survival to the patients with hematologic malignancies.  Chronic graft-versus-host disease (GVHD) is one of major problems for the long-survivors after allo-HCT.  Dysregulation of immune reconstitution has been reported to be involved in the pathogenesis of chronic GVHD.  Differences of immune reconstitution between cord blood transplantation (CBT) and unrelated bone marrow transplantation (uBMT) remain unclear in long-term survivors.  We investigated immune reconstitution in patients who survive for more than 2 years after CBT (n=21) or uBMT (n=20) without relapse of underlying disease.

    Materials and Methods

    Using flowcytomeric analysis of peripheral blood, we investigated immune reconstitution of T cells, B cells, and NK cells between CBT and uBMT patients.  We collected clinical data regarding allo-HCT and examined the relation of immune reconstitution to the development of chronic GVHD.

    Results

    Between CBT and uBMT patients, we found significant differences in absolute cell number of CD8+ as well as CD19+ cell and CD4/CD8 ratio even more than 2 years after allo-HCT.  Among uBMT patients, absolute cell number of naïve CD4+ cell was significantly lower in patients with chronic GVHD.  In addition, we found significant differences in absolute cell number of CD19+ cell, especially naïve B cell between patients with and without chronic GVHD in both CBT and uBMT patients.

    Conclusion

    These results suggest that differences of immune recovery between CBT and uBMT patients may exist even in patients who survive for more than 2 years and might be related to the development of chronic GVHD.

    Keywords: Immune reconstitution, Cord blood transplantation, Unrelated bone marrow transplantation, Chronic GVHD
  • Ladan Nekoohesh, Mohammad Ghahremani, Shahrbanoo Rostami, Mohsen Nikbakht, Leila Nekoohesh, Roozbeh Naemi, Saeed Mohammadi, Laya Ghadyaninejad, Seyed Asadollah Mousavi, Mohammad Vaezi, Kamran Alimoghaddam, Bahram Chahardouli* Pages 11-18
    Background

    The present study investigated the patients with Chronic Myeloid Leukemia in chronic phase (CP-CML) who had beenon the first- line Imatinib Mesylate (IM) therapy for a period of 84 months.

    Materials and Methods

    This retrospective study was conducted in 295 newly-diagnosed CP-CML patients(age >18 years)who were admitted to the Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran during 1 January 2009 to 30 December 2016. Response to treatment was evaluated by molecular response assessment. Rates of IM dose adjustment, switching to another drug therapy, Progression to Accelerate Phase (AP) and Blastic Crisis (BC) and long-term outcomes included Overall Survival (OS) and Progression Free Survival (PFS) were assesed.

    Results

    Patients’ average age was 41.7 years, and 52.9% were male. 44.4% of patients at the month 18 achieved Major Molecular Response (MMR). Progression to AP/BC occurred in 26 patients during 84 months, and the estimated rate of OS and PFS were 71.83 and 74.48, respectively. Among the patients who didn’t achieve MMR at month 18 , 61 patients were treated with IM ( 400 mg /day), and then after month 18, 24(39.3%) of whom  achieved MMR. Dose adjustments occurred in 60 patients (20.33%). IM dose increases were observed in 53 patients who didn’t achive optimal response to imatinib or loss of optimal response. IM dose decreases were observed in 7 patients. 25 (8.47%)  patients were switched to a different Tyrosine Kinase Inhibitor (TKI). Most of TKI changes(n=21) happened in patients who didn’t achieve optimal response to IM and for the 4 patients TKI changes were owing to adverse events of IM. Among the patients undergoing change in treatment, 24(43.75%) patient achieved MMR.

    Conclusion

    Our data showed the high effectiveness of the change in the treatment of IM-resistant condition. Moreover, our finding suggests that imatinib be effective in Iranian patients after a long period of time compared to the referenced studies.

    Keywords: Chronic myeloid leukemia, Imatinib, Resistance
  • Samira Abbasi, Mohsen Shahriari, Majid Ghanavat, Sedigheh Talakoub, Fatemeh Sadat Mosavi Asl, Zeinab Hemati* Pages 19-26
    Background

    Thalassemia as a chronic disease could affect different aspects of a patient’s life. On the other hand, when encountering the symptoms of a chronic disease as a stressful factor, the coping strategy of the adolescents and their families could have an important role in the quality of life of these patients. The present study was conducted to determine the relation between different aspects of quality of life with coping styles in the adolescents with thalassemia in comparison to a healthy control group.

    Materials and Methods

    The present study is a case-control research in 2017. Studied samples were 200 adolescents with thalassemia and healthy adolescents. Data gathering tools were demographic characteristics checklist and the coping style and quality of life questionnaire by the World Health Organization. Data were analyzed by SPSS 20 using independent t-test, linear regression and correlation coefficients.

    Conclusion

    Results of Pearson statistical test showed a significant relation between the total mean score of quality of life and its physical, social and mental aspects with emotion-oriented coping style (p<0.01). Also a direct significant relation was observed between the total mean score of quality of life and its social and physical aspects with problem-oriented coping style(p<0.01).

    Conclusion

    According to the results of the present study, a significant relation exists between some aspects of quality of life and some of the coping styles in adolescents with thalassemia. Therefore, educating the adolescents and their families for paying attention to the coping style for stressful factors and preparing these adolescents for passing toward the youth period, which could be challenging for them, are highly recommended.

    Keywords: Thalassemia, Adolescents, Quality of life, Coping style
  • Wafaa El Neanaey, Rania Swelem, Omar Ghallab, Sara Abu Shelou Pages 27-37
    Background

    The present work aimed to investigate the expression of CD160/ CD200 in CLL and other mature B-cell neoplasms (MBN) and their use as an additional diagnostic tool for differentiating CLL from other MBN.

    Materials and Methods

    Using flowcytometry, we detected the expression of CD160 &CD200 on B-cells from 30 CLL patients, 30 other MBN patients in addition to 20 controls. CDs160/200 measurements were determined as a percentage expression (≥20% was considered positive) and as a ratio of the mean fluorescence intensities (MFIR) of leukemic cells/controls and were considered positive when the ratios were ≥2 and 20, respectively.

    Results

    90% and 100% of the CLL group expressed CDs160/200 in comparison to 60% and 63.3% of other MBN (p=0.007, p<0.001) respectively. By MFIR; 96.7% and 50% of our CLL group expressed CDs160/200 in comparison to 76.7% and 30% of other MBN, respectively. CDs160/ 200 were not expressed on the controls. Positive co-expression of CD160 and CD200 was found in 90% of the CLL cases, 60% of HCL patients & only in 40% of B-NHL. However, double negative expression of both markers was found only in 24% of the B-NHL patients.

    Conclusion

    CD160 with CD200 can be used as additional diagnostic markers to the available routine panel to differentiate between B-CLL & other non-specified B-NHL patients.

    Keywords: CLL, MBN, CD200, CD160, Flowcytometry
  • Hayedeh Javadzadeh Shahshahani*, Azam Hayati Pages 38-44
    Background

    Blood group testing is an important part of supplying safe blood components in blood transfusion centers. Blood group discrepancy develops when reactions in forward grouping do not correspond with reverse grouping or if the preceding and recent results do not match. This study aimed to evaluate ABO blood group discrepancies among blood donors of Yazd, Iran.

    Materials and Methods

    In this cross-sectional study, data of blood donors were obtained from the integrated database of Yazd Blood Transfusion Center during a period of eight years (2010 – 2017). Tube testing was used for determining the ABO blood groups. A serological workup was performed for diagnosis and determination of the discrepancy. Confirmation of the results was accomplished by the reference laboratory of immunohematology.

    Results

    Blood group discrepancies were detected in 130 (0.04%) out of 322,222 donations. Technical/Clerical errors leading to ABO discrepancy were noticed in 12 (9.3%) cases. The most frequent cause of ABO discrepancies in forward grouping was subgroups of A Antigen (44.6%) and in reverse grouping was cold autoantibody (23.9%). There were 11 (8.4%) cases with alloantibodies. Two blood donors with rare Bombay phenotype and p blood group were also identified.

    Conclusion

    For minimizing Technical/Clerical errors, accurate blood donor or sample identification programs should be implemented. All cases of blood group discrepancies should be carefully investigated, and blood donors should be informed appropriately.

    Keywords: Blood group discrepancy, Blood donors, ABO blood typing
  • Masumeh Sanaei, Fraidoon Kavoosi*, Zahra Esmi Pages 45-55
    Background

    Aberrant methylation and histone deacetylation of tumor suppressor genes (TSGs) are the most epigenetic alterations involving in tumorigenesis. Overexpression of DNA methyltransferases (DNMTs) and histone deacetylase 1 (HDAC1) have been reported in several cancers. The reversion of hypermethylation and deacetylation by epi-drugs such as 5-aza-2′-deoxycytidine (5-AZA-CdR) and vorinostat (SAHA) can restore normal expression of TSGs. Previously, we reported that 5-AZA-CdR and valproic acid (VPA) can inhibit DNMT1 in hepatocellular carcinoma (HCC). The aim of this study was to investigate the effect of 5-AZA-CdR in combination to and in comparison with SAHA on DNMT1, DNMT3a, DNMT3b, histone deacetylase 1 (HDAC1), glutathione S-transferase 1 (GSTP1) and suppressor of cytokine signaling 1 (SOCS1)  genes expression, cell growth inhibition and apoptotic induction in hepatocellular LCL-PI 11 cell line.

    Materials and Methods

    The cells were treated with 5-AZA-CdR and SAHA and then MTT assay, cell apoptosis assay and Real-time quantitative RT-PCR (qRT-PCR) were done.

    Results

    Both agents indicated significant inhibitory and apoptotic effect (P< 0.001). The apoptotic effect of SAHA was more than that of 5-Aza-CdR. The result of qRT-PCR indicated that 5-Aza-CdR decreased DNMT1, DNMT3a, DNMT3b and increased GSTP1and SOCS1 genes expression and SAHA decreased HDAC1 and increased GSTP1 and SOCS1 genes expression significantly. Maximal apoptosis and genes expression were seen with combined treatment.

    Conclusion

    5-AZA-CdR and SAHA down-regulated DNMT1, DNMT3a, DNMT3b, and HDAC1 and up-regulated GSTP1 and SOCS1 gene expression by which inhibited cell viability and induced apoptosis, suggesting that they could be used in the treatment of HCC.

    Keywords: Epi-drugs, Tumor suppressor genes, Cancer
  • Amir Abbasnezhad, Mehdi Habibi, Babak Abdolkarimi, Soodabeh Zare, Ezatollah Fazeli Moghadam, Razieh Choghakhori Pages 56-71
    Background

    To investigate the serum levels of 25(OH)D and minerals in adults and children with haemophilia A, and the possible association of these factors with Pediatric Haemophilia/Haemophilia Activities List (PedHAL/HAL), Haemophilia Joint Health Score (HJHS) and Haemophilia-specific quality of life (QoL) index this case-control study was conducted.

    Materials and Methods

    Eighty five haemophilia A patients (HP) registered in Hemophilia Society of Lorestan province were recruited. Along with HP, sex and age matched healthy controls (HCs) were recruited. Linear regression was used to evaluate the possible relation between biochemical factors and other variables. One-way analysis of variance (ANOVA) was used to compare the biochemical factors between three or more independent groups.

    Results

    Results indicated that serum zinc, phosphorus and magnesium were significantly lower, whereas, serum level of alkaline phosphatase (ALP) was statistically higher in HP compared with HCs. Other biochemical factors including calcium and parathyroid hormone (PTH) were not different between groups. Serum 25(OH) D was lower only in children with haemophilia and not in adults. Percentage of subjects who were vitamin D deficient was higher in HP vs. HCs (57.6% vs. 35.3%), and also this rate was higher in children with haemophilia vs. adults (77.8% vs. 48.3%). Lower serum concentrations of assessed minerals and vitamin D were associated with lower physical activity, poor QoL and worst joint health, and these associations were stronger in children.

    Conclusion

    Present study indicated that serum levels of vitamin D and minerals were low in HP, and these low levels were associated with poor QoL, lower physical activity and worst joint health.

    Keywords: Haemophilia, vitamin D, Pediatric Haemophilia, Haemophilia Activities List, Haemophilia Joint Health Score, Haemophilia-specific quality of life
  • Mat Jusoh Siti Asmaa, Hamid Ali Al Jamal, Abdul Rahim Hussein, Badrul Hisham Yahaya, Azlan Husin, Rosline Hassan, Faezahtul Arbaeyah Hussain, Shaharum Shamsuddin, Muhammad Farid Johan Pages 72-92
    Background

    Acute myeloid leukemia (AML) is the most common form of acute leukemias in adults which is clinically and molecularly heterogeneous. Several risk and genetic factors have been widely investigated to characterize AML. However, the concomitant epigenetic factors in controlling the gene expression lead to AML transformation was not fully understood. This study was aimed to identify epigenetically regulated genes in AML cell lines induced by epigenetic modulating agents, Trichostatin A (TSA) and 5-Azacytidine (5-Aza).

    Methods

    MV4-11 and Kasumi 1 were treated with TSA and/or 5-Aza at IC50concentration. Gene expression profiling by microarray was utilized using SurePrint G3 Human Gene Expression v3. Gene ontology and KEGG pathway annotations were analyzed by DAVID bioinformatics software using EASE enrichment score. mRNA expression of the differentially expressed genes were verified by quantitative real time PCR.

    Results

    Gene expression analysis revealed a significantchanges in the expression of 24,822, 15,720, 15,654 genes in MV4-11 and 12,598, 8828, 18,026 genes in Kasumi 1, in response to TSA, 5-Aza and combination treatments, respectively, compared to non-treated (p<0.05). 7 genes (SOCS3,TUBA1C, CCNA1, MAP3K6, PTPRC, STAT6and RUNX1) and 4 genes (ANGPTL4, TUBB2A, ADAM12and PTPN6) shown to be predominantly expressed in MV4-11 and Kasumi 1, respectively (EASE<0.1). The analysis also revealed phagosome pathway commonly activated in both cell lines.

    Conclusion

    Our data showed a distinct optimal biological characteristic and pathway in different types of leukemic cell lines. These finding may help in the identification of cell-specific epigenetic biomarker in the pathogenesis of AML.

    Keywords: Acute myeloid leukemia, Epigenetics, Histone deacetylase inhibitors, 5-Azacytidine, Gene expression