Large granular lymphocytic leukemia coexists with myeloid clones and myelodysplastic syndrome
Leukemia, Published online: 17 October 2019; doi:10.1038/s41375-019-0601-yLarge granular lymphocytic leukemia coexists with myeloid clones and myelodysplastic syndrome (Source: Leukemia)
Source: Leukemia - October 17, 2019 Category: Hematology Authors: Jibran Durrani Hassan Awada Ashwin Kishtagari Valeria Visconte Cassandra Kerr Vera Adema Yasunobu Nagata Teodora Kuzmanovic Sanghee Hong Bhumika Patel Aziz Nazha Alan Lichtin Sudipto Mukherjee Yogen Saunthararajah Hetty Carraway Mikkael Sekeres Jaroslaw P Source Type: research

Restrictive versus Liberal Transfusion Strategies in Myelodysplastic Syndrome and Beyond
Publication date: Available online 13 October 2019Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Lindsay Wilde, Jonathan PanAbstractAnemia is the most common cytopenia seen in the myelodysplastic syndromes (MDS). The majority of patients with MDS will require red blood cell (RBC) transfusions during the course of their disease. However, unlike many other disease groups, there is no consensus on the optimal strategy for RBC transfusion in this patient population. In this article, we review the data supporting the use of restrictive transfusion strategies in multiple patient populations and discuss the current lite...
Source: Clinical Lymphoma Myeloma and Leukemia - October 15, 2019 Category: Cancer & Oncology Source Type: research

Exploratory Study of MYD88 L265P, Rare NLRP3 Variants, and Clonal Hematopoiesis Prevalence in Patients With Schnitzler Syndrome
ConclusionA shared molecular mechanism accounting for the pathogenesis of inflammation in SchS remains elusive. Clonal hematopoiesis is not associated with other somatic mutations found in individuals with SchS or aCAPS. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - October 14, 2019 Category: Rheumatology Authors: Shelly Pathak, Dorota M. Rowczenio, Roger G. Owen, Gina M. Doody, Darren J. Newton, Claire Taylor, Jan Taylor, Catherine Cargo, Philip N. Hawkins, Karoline Krause, Helen J. Lachmann, Sinisa Savic Tags: Brief Report Source Type: research

Restrictive versus Liberal Transfusion Strategies in Myelodysplastic Syndrome and Beyond
Anemia is the most common cytopenia seen in the myelodysplastic syndromes (MDS). The majority of patients with MDS will require red blood cell (RBC) transfusions during the course of their disease. However, unlike many other disease groups, there is no consensus on the optimal strategy for RBC transfusion in this patient population. In this article, we review the data supporting the use of restrictive transfusion strategies in multiple patient populations and discuss the current literature regarding transfusion management in patients with MDS. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - October 13, 2019 Category: Hematology Authors: Lindsay Wilde, Jonathan Pan Tags: Review Article Source Type: research

Comparative Effectiveness of Busulfan/Cyclophosphamide versus Busulfan/Fludarabine Myeloablative Conditioning for Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome
ConclusionWe confirmed that myeloablative Bu/Flu conditioning has comparable clinical and QOL outcomes to Bu/Cy. (Source: Hematology Oncology and Stem Cell Therapy)
Source: Hematology Oncology and Stem Cell Therapy - October 12, 2019 Category: Cancer & Oncology Source Type: research

Treosulfan or busulfan plus fludarabine as conditioning treatment before allogeneic haemopoietic stem cell transplantation for older patients with acute myeloid leukaemia or myelodysplastic syndrome (MC-FludT.14/L): a randomised, non-inferiority, phase 3 trial
Publication date: Available online 9 October 2019Source: The Lancet HaematologyAuthor(s): Dietrich Wilhelm Beelen, Rudolf Trenschel, Matthias Stelljes, Christoph Groth, Tamás Masszi, Péter Reményi, Eva-Maria Wagner-Drouet, Beate Hauptrock, Peter Dreger, Thomas Luft, Wolfgang Bethge, Wichard Vogel, Fabio Ciceri, Jacopo Peccatori, Friedrich Stölzel, Johannes Schetelig, Christian Junghanß, Christina Grosse-Thie, Mauricette Michallet, Hélène Labussiere-WalletSummaryBackgroundFurther improvement of preparative regimens before allogeneic haemopoietic stem cell transplantation (HSCT) ...
Source: The Lancet Haematology - October 11, 2019 Category: Hematology Source Type: research

Natural Killer Cells in Myeloid Malignancies: Immune Surveillance, NK Cell Dysfunction, and Pharmacological Opportunities to Bolster the Endogenous NK Cells
Natural killer (NK) cells are large granular lymphocytes involved in our defense against certain virus-infected and malignant cells. In contrast to T cells, NK cells elicit rapid anti-tumor responses based on signals from activating and inhibitory cell surface receptors. They also lyse target cells via antibody-dependent cellular cytotoxicity, a critical mode of action of several therapeutic antibodies used to treat cancer. A body of evidence shows that NK cells can exhibit potent anti-tumor activity against chronic myeloid leukemia (CML), acute myeloid leukemia (AML), and myelodysplastic syndromes (MDS). However, disease-...
Source: Frontiers in Immunology - October 11, 2019 Category: Allergy & Immunology Source Type: research

Prevalence of Paroxysmal Nocturnal Hemoglobinuria Clones in Myeloproliferative Neoplasm Patients: A Cross-Sectional Study
ConclusionThe prevalence of PNH clones in MPN is similar to that described in myelodysplastic syndromes. Whether PNH clones influence MPN phenotype and complications should be studied prospectively in larger patient cohorts and over long-term follow-up. (Source: Clinical Lymphoma Myeloma and Leukemia)
Source: Clinical Lymphoma Myeloma and Leukemia - October 10, 2019 Category: Cancer & Oncology Source Type: research

Association of uric acid levels before start of conditioning with mortality after alloSCT: a prospective, non-interventional study of the EBMT Transplant Complication Working Party.
ix H, Duarte RF, Basak GW Abstract Uric acid is a danger signal contributing to inflammation. Its relevance to allogeneic stem cell transplantation derives from preclinical models where the depletion of uric acid led to improved survival and reduced graft-versus-host disease. In a clinical pilot trial, peri-transplant uric acid depletion reduced acute graft-versus-host disease incidence. This prospective international multicenter study aimed to investigate the association of uric acid serum levels before start of conditioning with allogeneic stem cell transplantation outcome. We included patients with acute leukem...
Source: Haematologica - October 10, 2019 Category: Hematology Authors: Penack O, Peczynski C, van der Werf S, Finke J, Ganser A, Schoemans H, Pavlu J, Niittyvuopio R, Schroyens W, Kaynar L, Blau IW, van der Velden W, Sierra J, Cortelezzi A, Wulf G, Turlure P, Rovira M, Ozkurt Z, Pascual-Cascon MJ, Moreira MC, Clausen J, Grei Tags: Haematologica Source Type: research

Glasdegib for the treatment of adult patients with newly diagnosed acute myeloid leukemia or high-grade myelodysplastic syndrome who are elderly or otherwise unfit for standard induction chemotherapy.
In this report, we examine the preclinical development of glasdegib, its pharmacology and the clinical investigation that demonstrated its safety and efficacy, resulting in its approval. Additionally, we highlight ongoing investigation and future applications of this therapy. PMID: 31584572 [PubMed - in process] (Source: Drugs of Today)
Source: Drugs of Today - October 5, 2019 Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

Cancers, Vol. 11, Pages 1493: Antileukemic Efficacy in Vitro of Talazoparib and APE1 Inhibitor III Combined with Decitabine in Myeloid Malignancies
nn Fabarius Popp Malignant hematopoietic cells of myelodysplastic syndromes (MDS)/chronic myelomonocytic leukemias (CMML) and acute myeloid leukemias (AML) may be vulnerable to inhibition of poly(ADP ribose) polymerase 1/2 (PARP1/2) and apurinic/apyrimidinic endonuclease 1 (APE1). PARP1/2 and APE1 are critical enzymes involved in single-strand break repair and base excision repair, respectively. Here, we investigated the cytotoxic efficacy of talazoparib and APE1 inhibitor III, inhibitors of PARP1/2 and APE1, in primary CD34+ MDS/CMML cell samples (n = 8; 4 MDS and 4 CMML) and in primary CD34+ or CD34&min...
Source: Cancers - October 3, 2019 Category: Cancer & Oncology Authors: Kohl Flach Naumann Brendel Kleiner Weiss Seifarth Nowak Hofmann Fabarius Popp Tags: Article Source Type: research

Yttrium-90-labeled anti-CD45 antibody followed by a reduced-intensity hematopoietic cell transplantation for patients with relapsed/refractory leukemia or myelodysplasia.
In conclusion, the combination of 90Y-DOTA-BC8 with an allogeneic hematopoietic cell transplantation regimen was feasible and tolerable. This approach appears promising in this high-risk leukemia/myelodysplasia patient population with active disease. Clinicaltrials.gov identifier: NCT01300572. PMID: 31582553 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - October 3, 2019 Category: Hematology Authors: Vo P, Gooley TA, Rajendran JG, Fisher DR, Orozco JJ, Green DJ, Gopal AK, Haaf R, Nartea M, Storb R, Appelbaum FR, Press OW, Pagel JM, Sandmaier BM Tags: Haematologica Source Type: research

Long-term outcome of a randomized controlled study in patients with newly diagnosed severe aplastic anemia treated with antithymocyte globuline, cyclosporine, with or without G-CSF: a Severe Aplastic Anemia Working Party Trial from the European Group of Blood and Marrow Transplantation.
stic Anemia Working Party of the European Society for Blood and Marrow Transplantation Abstract This follow-up study of the randomized prospective trial included 192 patients with newly diagnosed severe aplastic anemia receiving Antithymoglobulin and Cyclosporine, with and without G-CSF. We aimed to evaluate the long-term effect of G-CSF on overall survival, event-free survival, probability of secondary myelodysplastic syndrome or acute myeloid leukemia, clinical paroxysmal nocturnal hemoglobinuria, relapse, avascular osteonecrosis and chronic kidney disease. The median follow-up was 11.7 years (10.9-12.5). Overal...
Source: Haematologica - October 3, 2019 Category: Hematology Authors: Tichelli A, Peffault de Latour R, Passweg J, Knol-Bout C, Socié G, Marsh J, Schrezenmeier H, Höchsmann B, Bacigalupo A, Samarasinghe S, Rovó A, Kulasekararaj A, Röth A, Eikema DJ, Bosman P, Bader P, Risitano A, Dufour C, Severe Aplastic Anemia Working Tags: Haematologica Source Type: research

The impact of iron chelation therapy on patients with lower/intermediate IPSS MDS and the prognostic role of elevated serum ferritin in patients with MDS and AML: A meta-analysis
Serum ferritin (SF) has been identified as a potential prognostic factor for patients undergoing stem cell transplantation, but the prognostic value of SF in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) patients and the impact of iron chelation therapy (ICT) on MDS patients are controversial. The present meta-analysis aimed to better elucidate these relationships. Three electronic databases were searched systematically to identify reports on the prognostic role of SF in MDS and AML patients, and those investigating the impact of ICT on prognosis of MDS patients. The hazard ratios (HRs) and its 95% conf...
Source: Medicine - October 1, 2019 Category: Internal Medicine Tags: Research Article: Meta-Analysis of Observational Studies in Epidemiology Source Type: research

1088PImpact of donor lymphocyte infusion in relapsing myeloid neoplasms post allogeneic hematopoietic stem cell transplantation
ConclusionsDLI was associated with a durable efficacy and low toxicity in pediatric patients with hematologic malignancies. However, larger studies and standardized approaches are required to identify the outcome predictors of this treatment modality.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest. (Source: Annals of Oncology)
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

285PSecond primary malignancies in patients with breast cancer
ConclusionsHM are the most frequent non BC SPM in p treated from BC; frequently they are therapy related neoplasms. Deescalating chemotherapy and radiotherapy in BC and finding genetic markers of early malignancy detection are mandatory.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest. (Source: Annals of Oncology)
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

GSE133828 Hematopoietic stem cell-restricted Cdx2 expression induces transformation to myelodysplasia and acute leukemia [RNASeq_Cdx2_secondaryAML]
Contributors : Therese Vu ; Steven W Lane ; Jasmin StraubeSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusThe caudal-related homeobox transcription factor CDX2 is ectopically expressed in the majority of patients with acute myeloid leukemia (AML). We generated an inducible transgenic mouse model whereby Cdx2 was specifically activated in HSCs . Cdx2 mice developed myelodysplastic syndrome (MDS) with progression to acute leukemia associated with stepwise acquisition of additional driver mutations. (Source: GEO: Gene Expression Omnibus)
Source: GEO: Gene Expression Omnibus - September 30, 2019 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research

GSE133680 Cdx2 driven acute myeloid leukemia is sensitive to therapy used in myeloid disease [RNASeq_Cdx2_AML_Azacitidine]
Contributors : Therese Vu ; Steven W Lane ; Jasmin StraubeSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusThe caudal-related homeobox transcription factor CDX2 is ectopically expressed in the majority of patients with acute myeloid leukemia (AML). We generated an inducible transgenic mouse model whereby Cdx2 was specifically activated in HSCs . Cdx2 mice developed myelodysplastic syndrome (MDS) with progression to acute leukemia associated with stepwise acquisition of additional driver mutations. (Source: GEO: Gene Expression Omnibus)
Source: GEO: Gene Expression Omnibus - September 30, 2019 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research

GSE133679 Hematopoietic stem cell-restricted Cdx2 expression induces transformation to myelodysplasia and acute leukemia [RNASeq_Cdx2_4weekspost_Tamoxifen]
Contributors : Therese Vu ; Steven W Lane ; Jasmin StraubeSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusThe caudal-related homeobox transcription factor CDX2 is ectopically expressed in the majority of patients with acute myeloid leukemia (AML). We generated an inducible transgenic mouse model whereby Cdx2 was specifically activated in HSCs. Cdx2 mice developed myelodysplastic syndrome (MDS) with progression to acute leukemia associated with stepwise acquisition of additional driver mutations. (Source: GEO: Gene Expression Omnibus)
Source: GEO: Gene Expression Omnibus - September 30, 2019 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research

GSE129828 DNA Methylation Identifies Genetically and Prognostically Distinct Subtypes of Myelodysplastic Syndromes
We report the identification of five subtypes of myelodysplastic syndromes (MDS) identified via unsupervised classification of DNA methylation (DNAm) profiles. Bisulfite padlock probe sequencing (BSPP) was used to measure DNAm of ~500,000 unique CpGs covering 140,749 non-overlapping regulatory regions across the genome in bone marrow DNA samples from 141 patients with MDS. Application of a non-negative matrix factorization (NMF) decomposition of DNAm profiles identified five consensus clusters described by five NMF components as the most stable grouping solution. (Source: GEO: Gene Expression Omnibus)
Source: GEO: Gene Expression Omnibus - September 30, 2019 Category: Genetics & Stem Cells Tags: Methylation profiling by high throughput sequencing Homo sapiens Source Type: research

Characteristics of long-term survivors with Myelodysplastic syndrome treated with 5-azacyditine. Results from the Hellenic 5-azacytidine Registry.
Publication date: Available online 28 September 2019Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Panagiotis T. Diamantopoulos, Vasiliki Pappa, Argiris Symeonidis, Ioannis Kotsianidis, Athanasios Galanopoulos, Helen Papadaki, Achilles Anagnostopoulos, George Vassilopoulos, Panagiotis Zikos, Eleftheria Hatzimichael, Maria Papaioannou, Aekaterini Megalakaki, Maria Kotsopoulou, Panagiotis Repousis, Maria Dimou, Eleni Solomou, Charalampos Pontikoglou, Georgios Kyriakakis, Dimitrios Tsokanas, Menelaos-Konstantinos PapoutselisAbstractHypomethylating agents have altered the prognosis of myelodysplastic syndrome (MDS) s...
Source: Clinical Lymphoma Myeloma and Leukemia - September 29, 2019 Category: Cancer & Oncology Source Type: research

Combination of Frailty Status and Comorbidity Score Improves the Stratification of Survival in Patients with Myelodysplastic Syndrome Due to Good Predictive Capability for Infection-Related Mortality
Publication date: Available online 28 September 2019Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Kazuki Sakatoku, Yasunobu Takeoka, Akiko Miura, Taku Araki, Yotaro Fujitani, Ryosuke Yamamura, Hirohisa Nakamae, Kensuke Ohta, Masayuki HinoAbstractBackgroundWe investigated the prognostic effects of frailty and its association with comorbidity in patients with myelodysplastic syndrome (MDS).MethodsThis retrospective analysis included 118 consecutive patients diagnosed with MDS. Frailty was evaluated using the clinical frailty scale (CFS). Comorbidity was classified using the Charlson comorbidity index (CCI) and MDS...
Source: Clinical Lymphoma Myeloma and Leukemia - September 29, 2019 Category: Cancer & Oncology Source Type: research

Cancers, Vol. 11, Pages 1463: Risk of Hematologic Malignant Neoplasms after Postoperative Treatment of Breast Cancer
This study aimed to analyze the role of postoperative treatment for BC in the development of subsequent HM. Using the French National Health Data System, we examined the HM risks in patients diagnosed with an incident primary breast cancer between 2007 and 2015, who underwent surgery as first-line treatment for BC. Main outcomes were acute myeloid leukemia (AML), Myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPNs), multiple myeloma (MM), Hodgkin’s lymphoma or non-Hodgkin’s lymphoma (HL/NHL), and acute lymphoblastic leukemia or lymphocytic lymphoma (ALL/LL). Analyses were censored...
Source: Cancers - September 29, 2019 Category: Cancer & Oncology Authors: Marie Joelle Jabagi Anthony Goncalves Norbert Vey Thien Le Tri Mahmoud Zureik Rosemary Dray-Spira Tags: Article Source Type: research

Characteristics of long-term survivors with Myelodysplastic syndrome treated with 5-azacyditine. Results from the Hellenic 5-azacytidine Registry.
Hypomethylating agents have altered the prognosis of myelodysplastic syndrome (MDS) so that long-term survival is now a feasible goal of treatment.We analyzed data from patients with MDS treated with 5-azacytidine recorded in the Hellenic 5-azacytidine registry. We divided patients, based on their survival after 5-azacytidine initiation (OST), in groups of long-term survivors (Q3 and P90 group with OST above the 3rd quartile and the 90th percentile of the whole group, respectively) and short-term survivors comprising the remaining patients, and compared the characteristics between the groups. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 28, 2019 Category: Hematology Authors: Panagiotis T. Diamantopoulos, Vasiliki Pappa, Argiris Symeonidis, Ioannis Kotsianidis, Athanasios Galanopoulos, Helen Papadaki, Achilles Anagnostopoulos, George Vassilopoulos, Panagiotis Zikos, Eleftheria Hatzimichael, Maria Papaioannou, Aekaterini Megala Tags: Original Study Source Type: research

Combination of Frailty Status and Comorbidity Score Improves the Stratification of Survival in Patients with Myelodysplastic Syndrome Due to Good Predictive Capability for Infection-Related Mortality
We retrospectively analyzed the prognostic effects of frailty and its association with comorbidity in patients with MDS at a single institute. The incidence of infection-related mortality progressively increased with frailty and comorbidity. Combining the evaluation of frailty and comorbidity might aid in more precise prediction of OS due to good predictive capability for infection-related mortality. (Source: Clinical Lymphoma, Myeloma and Leukemia)
Source: Clinical Lymphoma, Myeloma and Leukemia - September 28, 2019 Category: Hematology Authors: Kazuki Sakatoku, Yasunobu Takeoka, Akiko Miura, Taku Araki, Yotaro Fujitani, Ryosuke Yamamura, Hirohisa Nakamae, Kensuke Ohta, Masayuki Hino Tags: Original Study Source Type: research

The tale of lenalidomide clinical superiority over thalidomide and regulatory and cost-effectiveness issues
Abstract In April 2017, the National Sanitary Surveillance Agency (ANVISA-Brazil) approved lenalidomide (LEN) for multiple myeloma (MM) and myelodysplastic syndrome. ANVISA had rejected the first application in 2010, and denied a request for reconsideration in 2012. The reason for rejection was the lack of comparative effectiveness studies proving that LEN was more effective than thalidomide (THAL), a strictly controlled drug regulated by Federal law 10.651/2003 and dispensed to patients (at no costs) through public health system units and hospitals. ANVISA unexplained retreat on the LEN approval for marketing was an unque...
Source: Ciencia e Saude Coletiva - September 27, 2019 Category: Occupational Health Source Type: research

Transforming activities of the NUP98-KMT2A fusion gene associated with myelodysplasia and acute myeloid leukemia.
Abstract Inv(11)(p15q23) found in myelodysplastic syndromes and acute myeloid leukemia leads to expression of a fusion protein consisting of the N-terminal of nucleoporin 98 (NUP98) and the majority of the lysine methyltransferase 2A (KMT2A) transcript. To explore the transforming potential of this fusion we established inducible iNUP98-KMT2A transgenic mice. After a median latency of 80 weeks, over 90% of induced mice developed signs of disease, including anemia and reduced bone marrow cellularity, increased white blood cell numbers, extramedullary hematopoiesis, and multi-lineage dysplasia. Additionally, inducti...
Source: Haematologica - September 26, 2019 Category: Hematology Authors: Fisher JN, Thanasopoulou A, Juge S, Tzankov A, Bagger FO, Mendez MA, Peters AHFM, Schwaller J Tags: Haematologica Source Type: research

Efficacy and safety of iron chelator for transfusion-dependent patients with myelodysplastic syndrome: a meta-analysis.
Authors: Zhang J, Shi P, Liu J, Li J, Cao Y Abstract To systematically evaluate the efficacy and safety of iron chelators for transfusion-dependent patients with MDS. Thirteen cohort studies with 12,990 patients diagnosed with MDS were included in this study. According to m eta-analysis results transfusion-dependent MDS patients with secondary iron overload had a longer (HR = 0.52, 95%CI = 0.43-0.62, P 
Source: Hematology - September 25, 2019 Category: Hematology Tags: Hematology Source Type: research

[Research Articles] Muscarinic acetylcholine receptor regulates self-renewal of early erythroid progenitors
Adult stem and progenitor cells are uniquely capable of self-renewal, and targeting this process represents a potential therapeutic opportunity. The early erythroid progenitor, burst-forming unit erythroid (BFU-E), has substantial self-renewal potential and serves as a key cell type for the treatment of anemias. However, our understanding of mechanisms underlying BFU-E self-renewal is extremely limited. Here, we found that the muscarinic acetylcholine receptor, cholinergic receptor, muscarinic 4 (CHRM4), pathway regulates BFU-E self-renewal and that pharmacological inhibition of CHRM4 corrects anemias of myelodysplastic sy...
Source: Science Translational Medicine - September 25, 2019 Category: Biomedical Science Authors: Trivedi, G., Inoue, D., Chen, C., Bitner, L., Chung, Y. R., Taylor, J., Gönen, M., Wess, J., Abdel-Wahab, O., Zhang, L. Tags: Research Articles Source Type: research

Splicing factor mutant myelodysplastic syndromes: recent advances
Publication date: Available online 19 September 2019Source: Advances in Biological RegulationAuthor(s): Andrea Pellagatti, Jacqueline BoultwoodAbstractThe myelodysplastic syndromes (MDS) are common myeloid malignancies showing frequent progression to acute myeloid leukemia (AML). Pre-mRNA splicing is an essential cellular process carried out by the spliceosome. Mutations in splicing factor genes (including SF3B1, SRSF2, U2AF1 and ZRSR2) occur in over half of MDS patients and result in aberrant pre-mRNA splicing of many target genes, implicating aberrant spliceosome function in MDS disease pathogenesis. Recent functional st...
Source: Advances in Biological Regulation - September 21, 2019 Category: Biology Source Type: research

Prospective Phase 2 Study of Umbilical Cord Blood Transplantation in Adult Acute Leukemia and Myelodysplastic Syndrome
Hematopoietic stem cell transplantation from alternative donors is becoming an increasingly important option. Since HLA-mismatched umbilical cord blood transplantation (CBT) was introduced as a treatment option for adult hematological disease around 2000 [1,2], transplant outcomes with CBT have gradually improved [3]. However, because CB was assessed as an alternative donor source, second to unrelated volunteer donor in the earlier era, the patient's physical condition sometimes deteriorated with a prolonged donor search and the patient missed optimal transplant timing. (Source: Biology of Blood and Marrow Transplantation)
Source: Biology of Blood and Marrow Transplantation - September 20, 2019 Category: Hematology Authors: Seitaro Terakura, Tetsuya Nishida, Masashi Sawa, Tomonori Kato, Kotaro Miyao, Yukiyasu Ozawa, Akio Kohno, Yasushi Onishi, Noriko Fukuhara, Masanobu Kasai, Nobuharu Fujii, Hisayuki Yokoyama, Hiroatsu Iida, Nobuhiro Kanemura, Atsushi Fujieda, Hiroatsu Ago, Source Type: research

Decitabine promotes apoptosis in mesenchymal stromal cells isolated from patients with myelodysplastic syndromes by inducing reactive oxygen species generation.
Abstract Myelodysplastic syndromes (MDSs) are a group of clonal disorders of hematopoietic stem cells, resulting in ineffective hematopoiesis. Previous studies have reported that decitabine (DAC) plays an essential role in cell cycle arrest and cell death induction in multiple cell types. Nevertheless, the effect of decitabine on mesenchymal stromal cells derived from bone marrow of patients with MDSs is not completely clarified. Here, we explored the apoptotic and anti-proliferative effect of DAC on MSCs isolated from patients with MDSs. Treatment with DAC inhibited cell growth in a concentration- and time-depend...
Source: European Journal of Pharmacology - September 19, 2019 Category: Drugs & Pharmacology Authors: Wang L, Guo X, Guo X, Zhang X, Ren J Tags: Eur J Pharmacol Source Type: research

Iron Support in Erythropoietin Treatment in Myelodysplastic Syndrome Patients Affected by Low-Risk Refractory Anaemia: Real-Life Evidence from an Italian Setting.
Abstract Refractory anaemia (RA) among myelodysplastic syndrome (MDS) is associated with a partial functional iron deficit and may require transfusions. In low-risk lymphoma and solid tumour patients, iron support improves erythropoietin (EPO) cost-effectiveness in treating anaemia. The aim of this study is to see if oral sucrosomial iron support improves the cost-effectiveness of EPO treatment in MDS patients affected by low-risk RA. We treated patients with EPO only or with EPO plus oral sucrosomial iron or intravenous (i.v.) iron. The need for transfusions was lowest in the group taking oral iron (p = 0.016) or...
Source: Acta Haematologica - September 18, 2019 Category: Hematology Authors: Giordano G, Cutuli MA, Lucchesi A, Magnifico I, Venditti N, Vergalito F, Gasperi M, Di Marco R Tags: Acta Haematol Source Type: research

Cancers, Vol. 11, Pages 1373: Cytotoxicity and Differentiating Effect of the Poly(ADP-Ribose) Polymerase Inhibitor Olaparib in Myelodysplastic Syndromes
Graziani Maria Teresa Voso Myelodysplastic syndromes (MDS) are highly heterogeneous myeloid diseases, characterized by frequent genetic/chromosomal aberrations. Olaparib is a potent, orally bioavailable poly(ADP-ribose) polymerase 1 (PARP1) inhibitor with acceptable toxicity profile, designed as targeted therapy for DNA repair defective tumors. Here, we investigated olaparib activity in primary cultures of bone marrow mononuclear cells collected from patients with MDS (n = 28). A single treatment with olaparib induced cytotoxic effects in most samples, with median IC50 of 5.4 µM (2.0–24.8...
Source: Cancers - September 16, 2019 Category: Cancer & Oncology Authors: Isabella Faraoni Maria Irno Consalvo Francesca Aloisio Emiliano Fabiani Manuela Giansanti Francesca Di Cristino Giulia Falconi Lucio Tentori Ambra Di Veroli Paola Curzi Luca Maurillo Pasquale Niscola Francesco Lo-Coco Grazia Graziani Maria Teresa Voso Tags: Article Source Type: research

Pegylated liposomal doxorubicin for myeloid neoplasms
In this study, we first tested the role of Peg-Dox in the killing of myeloid cell lines and of primary myeloid leukemia cells. Then, a Peg-Dox-based protocol was used to treat patients with myeloid neoplasms. The results showed that the Peg-Dox and Peg-Dox-based protocols had a similar killing ability in myeloid cell lines and in primary myeloid leukemia cells compared to that of conventional doxorubicin. The complete remission rate was 87.5% and 100% for patients with refractory/relapsed acute myeloid leukemia and myelodysplastic syndrome with excess blasts, respectively, after treatment with Peg-Dox. All patients develop...
Source: Anti-Cancer Drugs - September 14, 2019 Category: Cancer & Oncology Tags: Clinical Reports Source Type: research

Guadecitabine (SGI-110): an investigational drug for the treatment of myelodysplastic syndrome and acute myeloid leukemia.
This article reviews the mechanism of action, pharmacology, safety profile and clinical efficacy of subcutaneous guadecitabine, a second generation DNA methylation inhibitor in development for the treatment of AML and MDS. Expert Opinion: Although guadecitabine did not yield improved complete remission (CR) rates and OS compared to the control arm in patients with treatment-naïve AML who were ineligible for intensive chemotherapy, subgroup analysis in patients who received ≥ 4 cycles of therapy demonstrated superior outcomes in favor of guadecitabine. Given its stability, ease of administration, safety profile and ...
Source: Expert Opinion on Investigational Drugs - September 14, 2019 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

A case report of severe bleeding due to lupus anticoagulant hypoprothrombinemia syndrome
We present a 74-years-old woman with history of myelodysplastic syndrome, admitted to the Emergency Department due to spontaneous mucocutaneous bleeding. Coagulation assays revealed prolonged prothrombin time and activated partial thromboplastin time with evidence of an immediate acting inhibitor. Antithrombotic therapy usage, drug ingestion, disseminated intravascular coagulation, liver dysfunction and sepsis were excluded. Patient was admitted for close monitoring and etiological evaluation. A comprehensive bleeding diathesis workup was performed showing factor II levels severely decreased and transient positive lupus an...
Source: Journal of Thrombosis and Thrombolysis - September 12, 2019 Category: Hematology Source Type: research

Updates on the hematological tumor microenvironment and its therapeutic targeting.
rer S Abstract In this review article, we present recent updates on the hematological tumor microenvironment following the 3rd Scientific Workshop on the Haematological Tumour Microenvironment and its Therapeutic Targeting organized by the European School of Hematology, which took place at the Francis Crick Institute in London in February 2019. This review article is focused on recent scientific advances highlighted in the invited presentations at the meeting, which encompass the normal and malignant niches supporting hematopoietic stem cells and their progeny. Therefore, for the sake of focus it does not discuss ...
Source: Haematologica - September 12, 2019 Category: Hematology Authors: Forte D, Krause DS, Andreeff M, Bonnet D, Méndez-Ferrer S Tags: Haematologica Source Type: research

Bartonella henselae bacteremia diagnosed post-mortem in a myelodysplastic syndrome patient.
This study involves a 49-year-old male, who for three years suffered with a myelodysplastic syndrome and who needed frequent blood transfusions. One day following a transfusion, he presented fever and abdominal pain. The fever became persistent and only improved temporarily with two cycles of intravenous ciprofloxacin. Nearly 120 days after beginning the second cycle of treatment, he had experienced a weight loss of 16 kg and recurring fever. Screening for fever of unknown origin was conducted, including Bartonella infection. No etiology could be found. The patient improved with an antimicrobial regimen composed of oral do...
Source: Revista do Instituto de Medicina Tropical de Sao Paulo - September 12, 2019 Category: Tropical Medicine Authors: Drummond MR, Visentainer L, Almeida AR, Angerami RN, Aoki FH, Velho PENF Tags: Rev Inst Med Trop Sao Paulo Source Type: research

MCM8- and MCM9 Deficiencies Cause Lifelong Increased Hematopoietic DNA Damage Driving p53-Dependent Myeloid Tumors
Publication date: 10 September 2019Source: Cell Reports, Volume 28, Issue 11Author(s): Malik Lutzmann, Florence Bernex, Cindy da Costa de Jesus, Dana Hodroj, Caroline Marty, Isabelle Plo, William Vainchenker, Marie Tosolini, Luc Forichon, Caroline Bret, Sophie Queille, Candice Marchive, Jean-Sébastien Hoffmann, Marcel MéchaliSummaryHematopoiesis is particularly sensitive to DNA damage. Myeloid tumor incidence increases in patients with DNA repair defects and after chemotherapy. It is not known why hematopoietic cells are highly vulnerable to DNA damage. Addressing this question is complicated by the paucity o...
Source: Cell Reports - September 11, 2019 Category: Cytology Source Type: research

5-Azacytidine modulates CpG methylation levels of EZH2 and NOTCH1 in myelodysplastic syndromes
ConclusionsA response to Aza is not associated with eradication of malignant clones, but rather with a stabilization of the clonal architecture. We suggest changes in CpG methylation levels ofEZH2 andNOTCH1 as potential targets of epigenetic response to Aza treatment which may also serve as useful biomarkers after clinical evaluation. (Source: Journal of Cancer Research and Clinical Oncology)
Source: Journal of Cancer Research and Clinical Oncology - September 10, 2019 Category: Cancer & Oncology Source Type: research

A rare case of acquired immunodeficiency associated with myelodysplastic syndrome
ConclusionThe hematological phenotype, somatic genomic instability, and response to HSCT MAC but not HSCT RIC deduced to a diagnosis of MDS type refractory cytopenia of children in this patient. His immunodeficiency was secondary to MDS due to somatic acquisition of homozygosity for known pathogenicRAG1 mutation. (Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - September 10, 2019 Category: Genetics & Stem Cells Authors: Juanjuan Li, Junhui Li, Jianguo Li, Hailan Yao, Fang Liu, James F Gusella, Xiaodong Shi, Xiaoli Chen Tags: ORIGINAL ARTICLE Source Type: research

5-Azacytidine modulates CpG methylation levels of EZH2 and NOTCH1 in myelodysplastic syndromes.
CONCLUSIONS: A response to Aza is not associated with eradication of malignant clones, but rather with a stabilization of the clonal architecture. We suggest changes in CpG methylation levels of EZH2 and NOTCH1 as potential targets of epigenetic response to Aza treatment which may also serve as useful biomarkers after clinical evaluation. PMID: 31506740 [PubMed - as supplied by publisher] (Source: Clin Med Res)
Source: Clin Med Res - September 10, 2019 Category: Research Authors: Gawlitza AL, Speith J, Rinke J, Sajzew R, Müller EK, Schäfer V, Hochhaus A, Ernst T Tags: J Cancer Res Clin Oncol Source Type: research

Prolonged response to recombinant human erythropoietin treatment in patients with myelodysplastic syndrome at a single referral centre in Brazil
CONCLUSIONS: Despite the wide use of EPO alfa in the treatment of anaemia in patients with MDS, the median response duration is approximately only 24 months. Our data provide encouraging results concerning the benefits of using EPO alfa for the improvement of the quality of life, as patients treated with EPO showed higher overall survival, event-free survival rates and longer response durations than have been previously described in the literature. (Source: Clinics)
Source: Clinics - September 9, 2019 Category: General Medicine Source Type: research

Prognostic value of DNMT3A mutations in myelodysplastic syndromes: a meta-analysis.
In this study, we conducted a meta-analysis to determine the prognostic effect of DNMT3A mutations in patients with MDS. Methods: Eligible studies from PubMed, Embase, Web of Science, Clinical Trials and the Cochrane Library were searched. Hazard ratios (HRs) and their 95% confidence intervals (CIs) for overall survival (OS) and leukemia-free survival (LFS) were pooled to assess the effect of DNMT3A mutations on the prognosis in MDS patients. Results: A total of 12 studies with 2236 patients were included in this meta-analysis. The pooled HRs for OS and LFS revealed that MDS patients with DNMT3A mutations had a significant...
Source: Hematology - September 5, 2019 Category: Hematology Tags: Hematology Source Type: research

Non-catalytic Roles of Tet2 Are Essential to Regulate Hematopoietic Stem and Progenitor Cell Homeostasis
Publication date: 3 September 2019Source: Cell Reports, Volume 28, Issue 10Author(s): Kyoko Ito, Joun Lee, Stephanie Chrysanthou, Yilin Zhao, Katherine Josephs, Hiroyo Sato, Julie Teruya-Feldstein, Deyou Zheng, Meelad M. Dawlaty, Keisuke ItoSummaryThe Ten-eleven translocation (TET) enzymes regulate gene expression by promoting DNA demethylation and partnering with chromatin modifiers. TET2, a member of this family, is frequently mutated in hematological disorders. The contributions of TET2 in hematopoiesis have been attributed to its DNA demethylase activity, and the significance of its nonenzymatic functions has remained ...
Source: Cell Reports - September 5, 2019 Category: Cytology Source Type: research

Conditioning regimen of 5-day decitabine administration for allogeneic stem cell transplantation in patients with myelodysplastic syndrome and myeloproliterative neoplasms
Owing to poor prognosis and limited therapeutic modalities, treatment of myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) has long been a challenge for researchers [1,2]. In recent years, allogeneic hematopoietic stem cell transplantation (allo-HSCT) has provided a potential curative therapy for patients with MDS and MDS/MPN. However, relapse, treatment-related death, and non-relapse mortality (NRM) – which are often related to graft-versus-host disease (GVHD)—remain major obstacles to universally successful transplantation. (Source: Biology of Blood and Marrow Transplantation)
Source: Biology of Blood and Marrow Transplantation - September 5, 2019 Category: Hematology Authors: Yi-Geng Cao, Yi He, Su-Dong Zhang, Zi-Xian Liu, Wei-Hua Zhai, Qiao-Ling Ma, Ai-Ming Pang, Jia-Ling Wei, Dong-Ling Yang, Yong Huang, Si-Zhou Feng, Er-Lie Jiang, Ming-Zhe Han Source Type: research

5-Formylcytosine and 5-hydroxymethyluracil as surrogate markers of TET2 and SF3B1 mutations in myelodysplastic syndrome, respectively.
Abstract PMID: 31488558 [PubMed - as supplied by publisher] (Source: Haematologica)
Source: Haematologica - September 5, 2019 Category: Hematology Authors: Gackowski D, Gawronski M, Kerr C, Radivoyevitch T, Zarakowska E, Starczak M, Abakir A, Ruzov A, Maciejewski JP, Olinski R Tags: Haematologica Source Type: research

Synergistic effects of PRIMA-1Met (APR-246) and Azacitidine in TP53-mutated myelodysplastic syndromes and acute myeloid leukemia.
ier S Abstract Myelodysplastic syndromes and acute myeloid leukemia with TP53 mutations are characterized by frequent relapses, poor or short responses, and poor survival with the currently available therapies including chemotherapy and 5-azacitidine. PRIMA-1Met (APR-246, APR) is a methylated derivative of PRIMA-1, which induces apoptosis in human tumor cells through restoration of the transcriptional transactivation function of mutant p53. We show here that low doses of APR on its own or in combination with 5-azacitidine reactivate the p53 pathway and induce an apoptosis program. Functionally, we demonstrate that...
Source: Haematologica - September 5, 2019 Category: Hematology Authors: Maslah N, Salomao N, Drevon L, Verger E, Partouche N, Ly P, Aubin P, Naoui N, Schlageter MH, Bally C, Miekoutima E, Rahmé R, Lehmann-Che J, Ades L, Fenaux P, Cassinat B, Giraudier S Tags: Haematologica Source Type: research