Safety and activity of selinexor in patients with myelodysplastic syndromes or oligoblastic acute myeloid leukaemia refractory to hypomethylating agents: a single-centre, single-arm, phase 2 trial
Publication date: August 2020Source: The Lancet Haematology, Volume 7, Issue 8Author(s): Justin Taylor, Xiaoli Mi, Alexander V Penson, Stella V Paffenholz, Kelsey Alvarez, Allison Sigler, Stephen S Chung, Raajit K Rampal, Jae H Park, Eytan M Stein, Martin S Tallman, Filiz Sen, Mithat Gönen, Omar Abdel-Wahab, Virginia M Klimek (Source: The Lancet Haematology)
Source: The Lancet Haematology - July 30, 2020 Category: Hematology Source Type: research

Treating myelodysplastic syndromes by nuclear transport inhibition
Publication date: August 2020Source: The Lancet Haematology, Volume 7, Issue 8Author(s): Katja Sockel (Source: The Lancet Haematology)
Source: The Lancet Haematology - July 30, 2020 Category: Hematology Source Type: research

Cytogenetic and cytokine profile in elderly patients with cytopenia
The number of elderly populations is on a continuous rise. A significant proportion of elderly patients suffer from anemia. Anemia has been identified as a risk factor for hospitalization and morbidity, especially in the elderly1. The cause of anemia could be multifactorial. Two-third of these patients have nutritional deficiencies and anemia of chronic disease. In one-third of patients, the cause of anemia is unknown. A significant proportion of these patients can represent early or undiagnosed myelodysplastic syndrome (MDS). (Source: Experimental Hematology)
Source: Experimental Hematology - July 30, 2020 Category: Hematology Authors: Dr. Shaila Mathai Kaniyattu, Dr. A Meenakshi, Dr. B Mohana Kumar, Dr. Karuna Ramesh Kumar, Dr. Shama Rao, Dr. D Prashanth Shetty, Dr. Vijith Shetty, Dr. K Jayaprakash Shetty, Dr. Padma K Shetty Source Type: research

Antibodies specific to ferritin light chain polypeptide are frequently detected in patients with immune ‑related pancytopenia.
Antibodies specific to ferritin light chain polypeptide are frequently detected in patients with immune‑related pancytopenia. Mol Med Rep. 2020 Sep;22(3):2012-2020 Authors: Hao S, Zhang Y, Hua L, Xie N, Xiao N, Wang H, Fu R, Shao Z Abstract Immuno-related pancytopenia (IRP) is characterized by pancytopenia resulting from bone marrow suppression or destruction mediated by auto‑antibodies. In our previous study, a K562 cDNA library was established, which was used to screen for seven possible auto‑antigens produced by hematopoietic cells in patients with IRP, including ferritin light chain (FTL...
Source: Molecular Medicine Reports - July 28, 2020 Category: Molecular Biology Tags: Mol Med Rep Source Type: research

New | phs001778.v1.p1 | Myelodysplastic Syndrome (MDS) in Humanized Mice
Myelodysplastic Syndrome (MDS) in Humanized Mice  (study page |release notes) (Source: dbGaP, the database of Genotypes and Phenotypes)
Source: dbGaP, the database of Genotypes and Phenotypes - July 21, 2020 Category: Genetics & Stem Cells Tags: StudyRelease Source Type: research

A frameshift variant in specificity protein 1 triggers superactivation of Sp1-mediated transcription in familial bone marrow failure [Genetics]
Inherited bone marrow failure (BMF) syndromes are a heterogeneous group of diseases characterized by defective hematopoiesis and often predisposing to myelodysplastic syndrome (MDS) and acute myelogenous leukemia. We have studied a large family consisting of several affected individuals with hematologic abnormalities, including one family member who died of acute leukemia.... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - July 21, 2020 Category: Science Authors: Hemanth Tummala, Amanda J. Walne, Findlay Bewicke-Copley, Alicia Ellison, Nikolas Pontikos, Maria G. Bridger, Ana Rio-Machin, Jasmin K. Sidhu, Jun Wang, Henrik Hasle, Jude Fitzgibbon, Tom Vulliamy, Inderjeet Dokal Tags: Biological Sciences Source Type: research

Haploidentical related donor vs matched sibling donor allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndrome aged over 50 years: A single ‐center retrospective study
We compared the transplant outcomes between HID and MSD transplants for AML and MSD aged ≥50 years. The results showed that HID transplant is feasible and safe for elderly AML/MDS patients. AbstractAllogeneic hematopoietic stem cell transplantation (allo ‐HSCT) is a potentially curative therapeutic option for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Increasing data suggest that haploidentical donor (HID) transplantation achieve comparable outcomes with HLA‐matched sibling donor (MSD) in adult AML/MDS. This re trospective study compared the outcomes of AML or MDS patients age ...
Source: Cancer Medicine - July 20, 2020 Category: Cancer & Oncology Authors: Jiafu Huang, Fen Huang, Zhiping Fan, Na Xu, Li Xuan, Hui Liu, Pengcheng Shi, Ling Jiang, Yu Zhang, Jing Sun, Qifa Liu Tags: ORIGINAL RESEARCH Source Type: research

Differences among hemoglobin thresholds for red blood cell transfusions in patients with hematological diseases in teaching hospitals: a real world data in Japan.
Abstract A hemoglobin (Hb) threshold level of 7 g/dL has been proposed for red blood cell (RBC) transfusion in patients with chronic anemia in the Japanese guideline since 2005. However, Hb thresholds for hematological diseases in clinical practice and factors responsible for higher Hb thresholds remain unclear. Hb thresholds were collected for patients with hematological diseases from 32 Japanese teaching hospitals. Uni- and multivariate analyses were used to analyze relationships between Hb threshold level and various patient and hospital factors. In total, 4996 units of RBC were transfused to 1054 patients...
Source: International Journal of Hematology - July 18, 2020 Category: Hematology Authors: Yokohama A, Okuyama Y, Ueda Y, Itoh M, Fujiwara SI, Hasegawa Y, Nagai K, Arakawa K, Miyazaki K, Makita M, Watanabe M, Ikeda K, Tanaka A, Fujino K, Matsumoto M, Makino S, Kino S, Takeshita A, Muroi K Tags: Int J Hematol Source Type: research

Co-occurrence of cohesin complex and Ras signaling mutations during progression from myelodysplastic syndromes to secondary acute myeloid leukemia.
e;guez JN, Martín-Nuñez G, Santos-Mínguez S, Miguel-García C, Benito R, Díez-Campelo M, Hernández-Rivas JM Abstract Myelodysplastic syndromes (MDS) are hematological disorders at high risk of progression to secondary acute myeloid leukemia (sAML). However, the mutational dynamics and clonal evolution underlying disease progression are poorly understood at present. To elucidate the mutational dynamics of pathways and genes occurring during the evolution to sAML, next generation sequencing was performed on 84 serially paired samples of MDS patients who developed sAML (discov...
Source: Haematologica - July 16, 2020 Category: Hematology Authors: Martín-Izquierdo M, Abáigar M, Hernández-Sánchez JM, Tamborero D, López-Cadenas F, Ramos F, Lumbreras E, Madinaveitia-Ochoa A, Megido M, Labrador J, Sánchez-Real J, Olivier C, Dávila J, Aguilar C, Rodríguez JN, Martín-Nuñez G, Santos-Mínguez S, Tags: Haematologica Source Type: research

Allogeneic hematopoietic cell transplantation in the management of GATA2 deficiency and pulmonary alveolar proteinosis.
Abstract Human hematopoiesis is critically dependent on the transcription factor GATA2. Patients with GATA2 deficiency typically present with myelodysplastic syndrome, reduced numbers of monocytes, NK cells and B cells, and/or opportunistic infections. Here, we present two families that harbor distinct GATA2 mutations with highly variable onset and course of disease. We discuss the use of allogeneic hematopoietic cell transplantation in these patients, especially as treatment for pulmonary alveolar proteinosis. PMID: 32682923 [PubMed - as supplied by publisher] (Source: Clinical Immunology)
Source: Clinical Immunology - July 16, 2020 Category: Allergy & Immunology Authors: van Lier YF, de Bree GJ, Jonkers RE, Roelofs JJTH, Ten Berge IJM, Rutten CE, Nur E, Kuijpers TW, Hazenberg MD, Zeerleder SS Tags: Clin Immunol Source Type: research

Patients of Myelodysplastic Syndrome with Mild/Moderate Myelofibrosis and a Monosomal Karyotype are Independently Associated with an Adverse Prognosis: Long-Term Follow-Up Data
(Source: Cancer Management and Research)
Source: Cancer Management and Research - July 15, 2020 Category: Cancer & Oncology Tags: Cancer Management and Research Source Type: research

4SC-202 induces apoptosis in myelodysplastic syndromes and the underlying mechanism.
In conclusion, 4SC-202 could induce apoptosis via the NF-κB pathway, and our present finding may provide a novel therapeutic strategy for MDS. PMID: 32655823 [PubMed] (Source: American Journal of Translational Research)
Source: American Journal of Translational Research - July 15, 2020 Category: Research Tags: Am J Transl Res Source Type: research

Clinical analysis and literature review of a case with the myelodysplastic syndrome/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis.
Conclusions: Our report provides a definite conceptual framework for a better understanding of the characteristics of MDS/MPN-RS-T. PMID: 32657243 [PubMed - in process] (Source: Hematology)
Source: Hematology - July 15, 2020 Category: Hematology Tags: Hematology Source Type: research

Erythropoietin Treatment Is Associated with Decreased Blood Glucose Levels in Hematologic Patients
Conclusion: ESA treatment for anemia is associated with lower blood glucose in hematologic patients. In those who also have diabetes mellitus, ESA might contribute to glucose control, and even to hypoglycemia. Glucose monitoring is thus advised. Further studies with both diabetic and nondiabetic patients are needed to clarify this association and underlying mechanisms.Acta Haematol (Source: Acta Haematologica)
Source: Acta Haematologica - July 13, 2020 Category: Hematology Source Type: research

Erythropoietin Treatment Is Associated with Decreased Blood Glucose Levels in Hematologic Patients.
Abstract BACKGROUND: Erythroid stimulating agents (ESAs) have pleiotropic effects, and in animal and human studies those exposed to high erythropoietin had lower blood glucose. OBJECTIVE: To determine the association between ESA and glucose in anemia-treated patients with myelodysplastic syndromes (MDS) or multiple myeloma (MM). PATIENTS AND METHODS: Patients' glucose levels were compared while on to while off ESA, and all served as their own controls. To test the association between ESA and blood glucose, we employed a linear mixed model, accounting for variability in the number of measurements for each...
Source: Acta Haematologica - July 13, 2020 Category: Hematology Authors: Oster HS, Gvili Perelman M, Kolomansky A, Neumann D, Mittelman M Tags: Acta Haematol Source Type: research

Incorporation of extracorporeal photopheresis into a reduced intensity conditioning regimen in myelodysplastic syndrome and aggressive lymphoma: results from ECOG 1402 and 1902.
CONCLUSIONS: These studies demonstrate that ECP/pentostatin/TBI is well tolerated and associated with adequate engraftment of neutrophils and platelets in patients with lymphomas and MDS. PMID: 32654201 [PubMed - as supplied by publisher] (Source: Transfusion)
Source: Transfusion - July 12, 2020 Category: Hematology Authors: Foss FM, Wang XV, Luger SM, Jegede O, Miller KB, Stadtmauer EA, Whiteside TL, Avigan DE, Gascoyne RD, Arber D, Wagner H, Strair RK, Hogan WJ, Sprague KA, Lazarus HM, Litzow MR, Tallman MS, Horning SJ Tags: Transfusion Source Type: research

Myeloablative intravenous busulfan-containing regimens for allo-HSCT in AML or MDS patients over 54  years old: combined results of three phase II studies.
Myeloablative intravenous busulfan-containing regimens for allo-HSCT in AML or MDS patients over 54 years old: combined results of three phase II studies. Int J Hematol. 2020 Jul 12;: Authors: Uchida N, Matsumoto K, Sakura T, Hidaka M, Miyamoto T, Eto T, Maeda Y, Murayama T, Fujishima N, Yoshimoto G, Morita K, Kishimoto J, Teshima T, Taniguchi S, Yamashita T, Mori SI, Akashi K, Harada M, Japan Study Group for Cell Therapy, Transplantation (JSCT) Abstract An optimal pretransplant conditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in older adults has not been es...
Source: International Journal of Hematology - July 12, 2020 Category: Hematology Authors: Uchida N, Matsumoto K, Sakura T, Hidaka M, Miyamoto T, Eto T, Maeda Y, Murayama T, Fujishima N, Yoshimoto G, Morita K, Kishimoto J, Teshima T, Taniguchi S, Yamashita T, Mori SI, Akashi K, Harada M, Japan Study Group for Cell Therapy, Transplantation (JSCT Tags: Int J Hematol Source Type: research

Targeting the Microenvironment in MDS: The Final Frontier
Myelodysplastic syndromes (MDS) are a heterogeneous group of malignant disorders of hematopoietic stem and progenitor cells (HSPC), mainly characterized by ineffective hematopoiesis leading to peripheral cytopenias and progressive bone marrow failure. While clonal dominance is nearly universal at diagnosis, most genetic mutations identified in patients with MDS do not provide a conspicuous advantage to the malignant cells. In this context, malignant cells alter their adjacent bone marrow microenvironment (BME) and rely on cell extrinsic factors to maintain clonal dominance. The profoundly disturbed BME favors the myelodysp...
Source: Frontiers in Pharmacology - July 9, 2020 Category: Drugs & Pharmacology Source Type: research

TLR2/6 signaling promotes the expansion of premalignant hematopoietic stem and progenitor cells in the NUP98-HOXD13 mouse model of MDS
The myelodysplastic syndromes are a group of hematopoietic stem and progenitor cell (HSPC) disorders characterized by abnormal hematopoiesis and a high risk of transformation to acute leukemia.1,2 Numerous prior studies have described enhanced innate immune signaling, and in particular, increased toll like receptor (TLR) signaling, in the CD34+ stem and progenitor cells of patients with MDS.3-11 This enhanced TLR signaling is thought to contribute to the ineffective hematopoiesis and cell death that is a prominent feature of lower-risk disease. (Source: Experimental Hematology)
Source: Experimental Hematology - July 8, 2020 Category: Hematology Authors: Darlene A. Monlish, Zev J. Greenberg, Sima T. Bhatt, Kathryn M. Leonard, Molly P. Romine, Qian Dong, Lauren Bendesky, Eric J. Duncavage, Jeffrey A. Magee, Laura G. Schuettpelz Source Type: research

Single-Nucleotide Polymorphism Array Technique Generating Valuable Risk-Stratification Information for Patients With Myelodysplastic Syndromes
Conclusions: SNP-A can help evaluate the prognosis of patients with MDSs and better assess the risk of disease progression for patients with ICUS. (Source: Frontiers in Oncology)
Source: Frontiers in Oncology - July 7, 2020 Category: Cancer & Oncology Source Type: research

Unrelated donor transplant recipients given Thymoglobuline have superior GRFS when compared to matched related donor recipients transplanted without ATG
Allogeneic hematopoietic stem cell transplantation (HSCT) is a cornerstone of curative therapy for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS)1,2. However, HSCT can be associated with significant morbidity and mortality, with major complications including infection, disease relapse and graft-versus-host disease (GVHD). Chronic GVHD in particular can severely impact the quality of life of survivors3. Its importance has been recognized by the increased reporting of composite outcomes such as GVHD-free, relapse-free survival (GRFS)4. (Source: Biology of Blood and Marrow Transplantation)
Source: Biology of Blood and Marrow Transplantation - July 4, 2020 Category: Hematology Authors: Jad Othman, Matthew Greenwood, John Moore, Stephen Larsen, Anne-Marie Watson, Chris Arthur, Abir Bhattacharyya, Ian Bilmon, Emily Blyth, Adam Bryant, Christian Bryant, Lindsay Dunlop, Keith Fay, John Gibson, Nada Hamad, Ian Kerridge, John Kwan, David Ma, Source Type: research

Evaluation of different scoring systems and gene mutations for the prognosis of myelodysplastic syndrome (MDS) in Chinese population
MDS is a heterogeneous disease with diverse clinical manifestations, and an effective prognostic evaluation tool for MDS patients is needed. To achieve more accurate prognosis assessment for Chinese MDS patients, here we examined several scoring systems and explored the implications of gene mutations. The prognostic conditions were stratified against three different score systems (International Prognostic Scoring System (IPSS), WHO Prognostic Scoring System (WPSS), and Revised International Prognostic Scoring System (IPSS-R)) were retrospectively applied to 110 de novo MDS patients in study cohort in our hospital and the p...
Source: Journal of Cancer - July 2, 2020 Category: Cancer & Oncology Authors: Meng-yi Du, Min Xu, Jun Deng, Lin Liu, Tao Guo, Ling-hui Xia, Yu Hu, Heng Mei Tags: Research Paper Source Type: research

GSE129691 Setd2 deficiency impaired erythroid differentiation and accelerated Myelodysplastic Syndrome(MDS) - associated leukemogenesis through S100A8 and S100A9
Contributors : Bingyi Chen ; Shubei Chen ; Chun-Hui Xu ; Xiao-Jian Sun ; Lan WangSeries Type : Genome binding/occupancy profiling by high throughput sequencing ; Expression profiling by high throughput sequencing ; Methylation profiling by high throughput sequencingOrganism : Mus musculusSetd2, the histone H3 lysine 36 methyltransferase, plays an important role in the pathogenesis of hematologic malignancies. The research on the role of Setd2 in leukemogenesis has made great progress, but its role in MDS is still unknown. Here, we knock out Setd2 in the NUP98-HOXD13 transgenic (NHD13 Tg) mouse, and demonstrate that loss of...
Source: GEO: Gene Expression Omnibus - July 2, 2020 Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Expression profiling by high throughput sequencing Methylation profiling by high throughput sequencing Mus musculus Source Type: research

Mortality among US military participants at eight aboveground nuclear weapons test series.
Conclusion: No statistically significant radiation associations were observed among 114,270 nuclear weapons test participants followed for up to 65 y. The 95% confidence limits were narrow and exclude mortality risks per unit dose that are two to four times those reported in other investigations. Significantly elevated SMRs were seen for mesothelioma and asbestosis, attributed to asbestos exposure aboard ships. PMID: 32602389 [PubMed - as supplied by publisher] (Source: International Journal of Radiation Biology)
Source: International Journal of Radiation Biology - July 1, 2020 Category: Radiology Tags: Int J Radiat Biol Source Type: research

Role Of TP53 mutations in predicting the clinical efficacy of hypomethylating therapy in patients with myelodysplastic syndrome and related neoplasms: a systematic review and meta-analysis
Abstract Hypomethylating agents (HMAs) are now a major treatment option for myelodysplastic syndrome (MDS) and related neoplasms, but 50% of patients still do not respond and realize poor outcomes. Mutational predictors of treatment efficacy attract continuous attention. Whether TP53 mutations can be used as predictors of HMA effectiveness has caused heated debate. Therefore, we performed a meta-analysis to investigate the predictive value of TP53 mutations to outcomes of HMA therapy in patients with MDS and related neoplasms. We systematically searched PubMed, Embase, the Cochrane Library, and the WanFang databases (publi...
Source: Clinical and Experimental Medicine - July 1, 2020 Category: Research Source Type: research

GSE141677 A new hypomethylating agent, OR-2100, resists degradation by cytidine deaminase, leading to favourable oral absorbability and ant-leukaemia effects
Contributors : Hiroshi Ureshino ; Yuki Kurahashi ; Tatsuro Watanabe ; Kazuharu Kamachi ; Yuki Fukuda-Kurahashi ; Nao Yoshida ; Naoko Hattori ; Yoshihiro Hayashi ; Kaoru Tohyama ; Seiji Okada ; Hironori Harada ; Toshikazu Ushijima ; Shinya KimuraSeries Type : Expression profiling by arrayOrganism : Homo sapiensDNA methyltransferase inhibitors have improved the prognosis of myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). However, these agents must be administered intravenously or subcutaneously because they are degraded easily by cytidine deaminase (CDA). OR2100 (OR21), an oligonucleotide comprising decitab...
Source: GEO: Gene Expression Omnibus - June 30, 2020 Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research

Population Pharmacokinetics and Exposure –Response of Luspatercept, an Erythroid Maturation Agent, in Anemic Patients With Myelodysplastic Syndromes
This report describes the population pharmacokinetics and exposure–response relationship of luspatercept in 260 patients with anemia due to myelodysplastic syndromes. Luspatercept displayed linear and time‐invariant pharmacokinetics over a dose range of 0.125–1.7 5 mg/kg administered subcutaneously once every 3 weeks. Body weight was the only clinically relevant covariate of luspatercept exposure, supporting the weight‐based dosing. The probability of achieving transfusion independence ≥ 8 weeks increased with time‐averaged luspatercept serum expos ure, reaching the plateau at doses...
Source: CPT: Pharmacometrics and Systems Pharmacology - June 30, 2020 Category: Drugs & Pharmacology Authors: Nianhang Chen, Nastya Kassir, Abderrahmane Laadem, Stephen E. Maxwell, Priya Sriraman, Ana Carolina Giuseppi, Steve Ritland, Peter G. Linde, Balasubrahmanyam Budda, Joseph G. Reynolds, Simon Zhou, Maria Palmisano Tags: Article Source Type: research

Immune checkpoints bone marrow expression as the predictor of clinical outcome in myelodysplastic syndrome: Immune checkpoints in myelodysplastic syndrome
Publication date: Available online 28 June 2020Source: Leukemia Research ReportsAuthor(s): Nikolai Tcvetkov, Artem Gusak, Elena Morozova, Ivan Moiseev, Vadim Baikov, Maria Barabanshikova, Kirill Lepik, Evgenyi Bakin, Julia Vlasova, Anna Osipova, Ludmila Zubarovskaya, Boris Afanasyev (Source: Leukemia Research Reports)
Source: Leukemia Research Reports - June 29, 2020 Category: Hematology Source Type: research

IGF ‑IR promotes clonal cell proliferation in myelodysplastic syndromes via inhibition of the MAPK pathway.
In conclusion, IGF‑IR may serve as a potential therapeutic target of MDS. PMID: 32583001 [PubMed - as supplied by publisher] (Source: Oncology Reports)
Source: Oncology Reports - June 27, 2020 Category: Cancer & Oncology Tags: Oncol Rep Source Type: research

Retrospective Evaluation of Relationship Between Iron Overload and Transplantation Complications in Pediatric Patient Who Underwent Allogeneic Stem Cell Transplantation Due to Acute Leukemia and Myelodysplastic Syndrome
Background: Hematopoietic stem cell transplantation (HSCT) is a curative therapy option for hematologic malignancies. Iron overload is common in this patient group and can impact short-term and long-term nonrelapse mortality. Study Design: Retrospective observational cohort study. Aims: To evaluate the effect of iron load on early and late HSCT outcomes in patients with acute leukemia and myelodysplasia to assess the necessity of reducing iron load. Patients and Methods: Sixty patients who underwent HSCT in pediatric stem cell transplantation unit between 2000 and 2012 were evaluated retrospectively. The patient...
Source: Journal of Pediatric Hematology Oncology - June 25, 2020 Category: Hematology Tags: Online Articles: Original Articles Source Type: research

Connecting the Dots From Fever of Unknown Origin to Myelodysplastic Syndrome: GATA2 Haploinsufficiency
We describe the case of a 17-year-old male presenting with features of nontuberculous mycobacterial infection, pulmonary fibrinoid granulomatous vasculitis, and myelodysplasia in the setting of a pathogenic GATA2 frameshift mutation confirmed by next-generation sequencing. The broad differential for GATA2 haploinsufficiency requires prompt recognition of key clinical features and laboratory abnormalities towards directing diagnosis and guiding appropriate and perhaps life-saving therapy. (Source: Journal of Pediatric Hematology Oncology)
Source: Journal of Pediatric Hematology Oncology - June 25, 2020 Category: Hematology Tags: Online Articles: Clinical and Laboratory Observations Source Type: research

High serum ferritin levels in newly diagnosed patients with myelodysplastic syndromes are associated with greater symptom severity.
We examined the association between serum ferritin (SF) levels and patient-reported functional aspects and symptoms, as measured by the EORTC QLQ-C30, in newly diagnosed patients with myelodysplastic syndromes (MDS). Analysis was conducted on 497 MDS patients who were classified in two groups based on the SF value of 1000 ng/mL. Clinically relevant differences of patient-reported functional and symptom scales were evaluated and classified as small, medium and large, based on established thresholds. Multivariable linear regression analysis was performed to account for potential confounding factors. Patients with SF of&...
Source: International Journal of Hematology - June 25, 2020 Category: Hematology Authors: Caocci G, Vignetti M, Patriarca A, Breccia M, Platzbecker U, Palumbo GA, Stauder R, Cottone F, Petranovic D, Voso MT, Tafuri A, Invernizzi R, Caers J, Luppi M, La Nasa G, Niscola P, Efficace F Tags: Int J Hematol Source Type: research

Menatetrenone facilitates hematopoietic cell generation in a manner that is dependent on human bone marrow mesenchymal stromal/stem cells.
Abstract Vitamin K2 in the form of menatetrenone has clinical benefits for osteoporosis and cytopenia. Given the dominant role of mesenchymal-osteolineage cells in the regulation of hematopoiesis, we investigated whether menatetrenone alters the hematopoiesis-supportive capability of human bone marrow mesenchymal stromal/stem cells (BM-MSCs). Menatetrenone up-regulated fibronectin protein expression in BM-MSCs without affecting their proliferation and differentiation capabilities. In addition, menatetrenone treatment of BM-MSCs enhanced generation of the CD34+ cell population in co-cultures through acceleration of...
Source: International Journal of Hematology - June 22, 2020 Category: Hematology Authors: Fujishiro A, Iwasa M, Fujii S, Maekawa T, Andoh A, Tohyama K, Takaori-Kondo A, Miura Y Tags: Int J Hematol Source Type: research

SPAG6 silencing induces autophagic cell death in SKM-1 cells via the AMPK/mTOR/ULK1 signaling pathway.
Authors: Zhang M, Luo J, Luo X, Liu L Abstract As a member of the cancer-testis antigen family, sperm-associated antigen 6 (SPAG6) has been reported to be associated with the pathogenesis of myelodysplastic syndromes (MDS). Previous studies have demonstrated that SPAG6 is upregulated in bone marrow from patients with MDS and MDS-transformed acute myeloid leukemia and that knockdown of SPAG6 expression levels suppressed proliferation and promote apoptosis and differentiation in SKM-1 cells. However, the association between SPAG6 and autophagy in SKM-1 cells remains unclear. Hence, the aim of the present study was to...
Source: Oncology Letters - June 17, 2020 Category: Cancer & Oncology Tags: Oncol Lett Source Type: research

Contribution of Aberrant Toll Like Receptor Signaling to the Pathogenesis of Myelodysplastic Syndromes
Toll like receptors (TLRs) are a family of pattern recognition receptors that play a central role in the innate immune response. These receptors are expressed on a wide variety of immune and non-immune cells, and they help shape the immune response to infection and injury through the recognition of pathogen-associated molecular patterns (PAMPs) as well as endogenous damage-associated molecular patterns (DAMPs). Accumulating evidence suggests that, in addition to regulating mature effector immune cells, TLRs can influence the immune response from the level of the hematopoietic stem cell (HSC). HSCs express TLRs, and exposur...
Source: Frontiers in Immunology - June 17, 2020 Category: Allergy & Immunology Source Type: research

Preconditioning absolute lymphocyte count and transplant outcomes in matched related donor allogeneic hematopoietic stem cell transplantation recipients with reduced-intensity conditioning and antithymocyte globulin treatment
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment option for several types of hematologic malignancies, including high-risk or relapsed acute leukemia and myelodysplastic syndrome (MDS), and some benign hematological diseases, such as severe aplastic anemia. Despite the significant progress in transplant technology and patient care that has been made since the 1960s, there are still obstacles that hinder achieving successful outcomes after allo-HSCT. (Source: Biology of Blood and Marrow Transplantation)
Source: Biology of Blood and Marrow Transplantation - June 16, 2020 Category: Hematology Authors: Go-Un Woo, Junshik Hong, Hyangseon Kim, Ja Min Byun, Youngil Koh, Dong-Yeop Shin, Inho Kim, Sung-Soo Yoon Source Type: research

Characterization of myelodysplastic syndromes progressing to acute lymphoblastic leukemia
We describe a series of 3 cases of MDS/CMML marked with evolution to acute lymphoblastic leukemia (ALL) and provide a comprehensive review of the 49 cases documented in the literature so far. These sporadic events have only been published as single-case reports or small series to date. Such atypical cases emphasize the possibility of major phenotypic switches arising at the leukemic stem cell (LSC) and/or early progenitor levels, as a consequence of epigenetic and genomic events driving these changes in the bone marrow niche. (Source: Annals of Hematology)
Source: Annals of Hematology - June 16, 2020 Category: Hematology Source Type: research

[Indications and management of hematologic microtransplantation: Recommendations of the French Society of Bone Marrow transplantation and cellular Therapy (SFGM-TC)].
our M Abstract Microtransplantation (MT) is based on injection of HLA-mismatched G-CSF mobilized hematopoietic stem cells, in combination with chemotherapy but without use of conditioning regimen nor immunosuppressive drugs. As a result, a transient microchimerism is induced without engraftment. Its efficacy relies both on host immune system stimulation (recipient versus tumor) and on a graft versus tumor effect. Data are scarce and concern mostly Asian patients with acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (HR-MDS). In comparison to conventional treatment without MT, higher complete rem...
Source: Bulletin du Cancer - June 16, 2020 Category: Cancer & Oncology Authors: Cornillon J, Carre M, Chalandon Y, Chevallier P, Coman T, Harif M, Labuissière-Wallet H, Mear JB, Picard C, Yakoub-Agha I, Srour M Tags: Bull Cancer Source Type: research

Transfusional iron overload in patients with myelodysplastic syndromes: A 10-year retrospective survey from a French general hospital.
Abstract We retrospectively assessed the characteristics of 165 MDS patients from our institution having received at least 20 RBC units. In the vast majority of them various comorbidities (range: 1-6 per patient) were registered including mainly cardiovascular disorders. Serum ferritin was over 1000 µg/L in about half of tested individuals. A chelator agent was initiated in 43.6% of patients (mainly low-risk MDS). Transformation in AML occurred in 46 cases (27.8%). Overall, 112 patients died during follow up. The cause of death was documented in 65 cases and included mainly MDS or AML resistance to therapy. ...
Source: Transfusion Clinique et Biologique - June 16, 2020 Category: Hematology Authors: Bauduer F, Recanzone H Tags: Transfus Clin Biol Source Type: research

Preconditioning Absolute Lymphocyte Count and Transplantation Outcomes in Matched Related Donor Allogeneic Hematopoietic Stem Cell Transplantation Recipients with Reduced-Intensity Conditioning and Antithymocyte Globulin Treatment
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment option for several types of hematologic malignancies, including high-risk or relapsed acute leukemia and myelodysplastic syndrome (MDS), and some benign hematological diseases, such as severe aplastic anemia. Despite the significant progress in transplant technology and patient care that has been made since the 1960s, there are still obstacles that hinder achieving successful outcomes after allo-HSCT. (Source: Biology of Blood and Marrow Transplantation)
Source: Biology of Blood and Marrow Transplantation - June 16, 2020 Category: Hematology Authors: Go-Un Woo, Junshik Hong, Hyangseon Kim, Ja Min Byun, Youngil Koh, Dong-Yeop Shin, Inho Kim, Sung-Soo Yoon Source Type: research

Battle of the clones: paroxysmal nocturnal hemoglobinuria vs myelodysplastic syndrome
(Source: Annals of Hematology)
Source: Annals of Hematology - June 13, 2020 Category: Hematology Source Type: research

GSE152262 A frameshift variant in the specificity protein 1 triggers superactivation of Sp1-mediated transcription in familial bone marrow failure
Contributors : Hemanth Tummala ; Tom Vulliamy ; Inderjeet DokalSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensInherited bone marrow failure (BMF) syndromes are a heterogeneous group of diseases characterised by defective hematopoiesis and often predispose to myelodysplastic syndrome (MDS) and acute myeloid leukemia. We have studied a large family consisting of several affected individuals with hematological abnormalities including one family member who died of acute leukemia. By whole exome sequencing, we identified a novel frameshift variant in the ubiquitously expressed transcripti...
Source: GEO: Gene Expression Omnibus - June 12, 2020 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research

Engineering of targeted megabase-scale deletions in human iPSCs
Recurrent chromosomal deletions are frequently associated with human diseases. Hematologic malignancies, in particular, often harbor focal deletions, most commonly at hemizygous state. These may drive disease by providing one of two hits towards complete gene inactivation or through haploinsufficiency of one or more genes. Deletion of the long arm of chromosome 7q (del7q) is a common cytogenetic abnormality in patients with hematologic malignancies, particularly myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). (Source: Experimental Hematology)
Source: Experimental Hematology - June 12, 2020 Category: Hematology Authors: Andriana G Kotini, Eirini P Papapetrou Source Type: research

Engineering of targeted megabase-scale deletions in human induced pluripotent stem cells
Recurrent chromosomal deletions are frequently associated with human diseases. Hematologic malignancies, in particular, often harbor focal deletions, most commonly in the hemizygous state. These may drive disease by providing one of two hits toward complete gene inactivation or through haplo-insufficiency of one or more genes. Deletion of the long arm of chromosome 7q (del7q) is a common cytogenetic abnormality in patients with hematologic malignancies, particularly myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). (Source: Experimental Hematology)
Source: Experimental Hematology - June 12, 2020 Category: Hematology Authors: Andriana G. Kotini, Eirini P. Papapetrou Tags: Original Research Source Type: research

Clinico-Hematological Profile of Paroxysmal Nocturnal Hemoglobinuria in Indian Patients: FLAER Flow Cytometry Based Experience from an Indian Tertiary Care Centre
AbstractPNH is a rare disease with wide spectrum of intra-vascular hemolysis and thrombosis to sub-clinical PNH clones. We aimed to study the clinico-hematological profile and clone size on granulocytes and monocytes of PNH patients classified as per International PNH Interest Group recommendations. A retrospective analysis of clinico-hematological profile of 112 PNH clone positive patients by FLAER based flow cytometry between January and September 2017 done and classified into classical PNH, PNH with aplastic anemia or myelodysplastic syndrome (PNH-AA/MDS) and sub-clinical PNH clones (PNH-sc). Of 112 patients, majority w...
Source: Indian Journal of Hematology and Blood Transfusion - June 10, 2020 Category: Hematology Source Type: research

The impact of transfusion burden and comorbidities on the prognosis of patients with myelodysplastic syndromes
Early comorbidity detection has been reported to be associated with treatment-related outcomes in several diseases. Two main goals of the present study were to investigate both the impact of comorbidities and transfusion frequencies on the survival and quality of life of patients with myelodysplastic syndromes (MDS). (Source: Transfusion and Apheresis Science)
Source: Transfusion and Apheresis Science - June 9, 2020 Category: Hematology Authors: Ahmet Sarici, Muhlis Cem Ar, Osman Yokus, Seniz Ongoren, Mesut Ayer, Sermin Altindal, Hilal Tan Koker, Omer Faruk Kuzu Source Type: research

Myelodysplastic syndromes in a pediatric patient with Cri du Chat syndrome with a ring chromosome 5.
Abstract Few hematological complications have previously been reported in association with Cri du Chat syndrome (CdCS). A case of myelodysplastic syndromes (MDS) in a pediatric patient with CdCS is herein presented. A 17-year-old female with CdCS caused by ring chromosome 5 was admitted to the hospital for investigation of a 1-month history of anemia. Based on the morphological findings of bone marrow, the patient was diagnosed with refractory cytopenia with multilineage dysplasia. The risk group was classified as intermediate-1 in the International Prognostic Scoring System (IPSS), and low in the revised IPSS. As...
Source: International Journal of Hematology - June 9, 2020 Category: Hematology Authors: Nozawa A, Ozeki M, Yasue S, Endo S, Kadowaki T, Ohnishi H, Muramatsu H, Hama A, Takahashi Y, Kojima S, Fukao T Tags: Int J Hematol Source Type: research

Ovarian tissue cryopreservation and transplantation prevents iatrogenic premature ovarian insufficiency: first 10 cases in China.
Conclusion: Regarding ovarian function, OTC and OTCT were successful and reliable in China's first cryobank. We expect to perform more retransplantations in the near future, which will add to the global data. PMID: 32508143 [PubMed - as supplied by publisher] (Source: Climacteric)
Source: Climacteric - June 8, 2020 Category: Geriatrics Authors: Ruan X, Cheng J, Korell M, Du J, Kong W, Lu D, Wu Y, Li Y, Jin F, Gu M, Duan W, Dai Y, Yin C, Yan S, Mueck AO Tags: Climacteric Source Type: research

Sonic hedgehog signaling pathway in Myelodysplastic Syndrome: abnormal activation and jervine intervention.
CONCLUSION: Shh signaling pathway of MDS patients is abnormally activated and participated in the occurrence and progression of MDS. Jervine intervention is a potential therapeutic strategy for MDS. PMID: 32526259 [PubMed - as supplied by publisher] (Source: Gene)
Source: Gene - June 8, 2020 Category: Genetics & Stem Cells Authors: Qin Y, Jiang M, Tuerxung N, Wang H, Zhao F, Zhen Y, Hao J Tags: Gene Source Type: research