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N Engl J Med 2020 01;382(2):140-151

From Service d'Hématologie Séniors, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris and Université Paris 7, Paris (P.F., L.A.), Service des Maladies du Sang, Hôpital Huriez, Centre Hospitalier Universitaire (CHU) de Lille, Lille (B.Q.), the Department of Internal Medicine, CHU Toulouse, Institut Universitaire du Cancer de Toulouse, Toulouse (O.B.-R.), and Université Cote d'Azur, Département d'Hématologie Clinique, CHU Nice, Nice (T.C.) - all in France; Medical Clinic and Policlinic 1, Hematology and Cellular Therapy, Leipzig University Hospital, Leipzig (U.P.), Klinik für Hämatologie, Onkologie, and Klinische Immunologie, Universitätsklinik Düsseldorf, Düsseldorf (U.G.), and Klinik und Poliklinik für Innere Medizin III, Technische Universität München, Munich (K.S.G.) - all in Germany; the Department of Haemato-Oncology, King's College London, London (G.J.M.), Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford (P.V.), and the Department of Haematology, Leeds Teaching Hospitals NHS Trust, Leeds (D.B.) - all in the United Kingdom; the Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston (G.G.-M.); Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto (R.B.); MDS Unit, Azienda Ospedaliero Universitaria Careggi, University of Florence, Florence (V.S.), the Department of Oncology and Hematology, S. Orsola-Malpighi University Hospital, Bologna (C.F.), the University of Pavia, Fondazione IRCCS Policlinico S. Matteo, Pavia (M.C.), the Hematology Unit, Santi Antonio e Biagio e Cesare Arrigo Hospital, Alessandria (F.S., V.G.), and Dipartimento Biomedicina e Prevenzione, University of Rome Tor Vergata, Rome (M.-T.V.) - all in Italy; the Hematology Department, University Hospital of Salamanca, Institute of Biomedical Research of Salamanca, Salamanca (M.D.-C.), Unidad de Hematología, Hospital Universitario Virgen del Rocío, Seville (J.F.F.), and the Department of Hematology, Hospital Universitario Cruces, Vizcaya (B.A.) - all in Spain; the Department of Hematology Science, School of Medicine, Ankara University, Ankara, Turkey (O.I.); the Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland (M.A.S.); the Department of Hematology, Algemeen Ziekenhuis Sint-Jan, Bruges (D.S.), and Universitair Ziekenhuis Gent, Ghent (D.M.) - both in Belgium; the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (A.E.D.); the Division of Hematology-Oncology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center (J.G.J.), and Albert Einstein College of Medicine (A.V.) - both in New York; the Department of Hematology, University Medical Center of Groningen, University of Groningen, Groningen, the Netherlands (E.V.); Stanford University Cancer Center, Stanford, CA (P.L.G.); the Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Stockholm (E.H.-L.); the Department of Internal Medicine, Yale School of Medicine, Yale University, New Haven, CT (A.M.Z.); Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center, Nashville (M.R.S.); Celgene, Summit, NJ (A.L., J.Z., A.R., D.R.D.); Celgene International, Boudry, Switzerland (A.B.); Acceleron Pharma, Cambridge, MA (P.G.L., M.L.S.); and Moffitt Cancer Center, Tampa, FL (R.S.K., A.F.L.).

Background: Patients with anemia and lower-risk myelodysplastic syndromes in whom erythropoiesis-stimulating agent therapy is not effective generally become dependent on red-cell transfusions. Luspatercept, a recombinant fusion protein that binds transforming growth factor β superfamily ligands to reduce SMAD2 and SMAD3 signaling, showed promising results in a phase 2 study.

Methods: In a double-blind, placebo-controlled, phase 3 trial, we randomly assigned patients with very-low-risk, low-risk, or intermediate-risk myelodysplastic syndromes (defined according to the Revised International Prognostic Scoring System) with ring sideroblasts who had been receiving regular red-cell transfusions to receive either luspatercept (at a dose of 1. Read More

Int J Lab Hematol 2019 Jun 27;41(3):345-352. Epub 2019 Feb 27.

Department of Pathology, Stanford University Medical Center, Stanford, California.

Introduction: Myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) is a rare disease in the 2016 revised World Health Organization (WHO) classification. Diagnostic criteria include the following: persistent thrombocytosis (>450 × 10 /L) with clustering of atypical megakaryocytes, refractory anemia, dyserythropoiesis with ring sideroblasts, and the presence of the spliceosome factor 3b subunit (SF3B1) mutation. It is unclear if anemia should be a required criterion for this diagnosis as cases which show all other features of MDS/MPN-RS-T but without anemia exist. Read More

Am J Hematol 2019 04 24;94(4):475-488. Epub 2019 Jan 24.

Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.

Disease Overview: Ring sideroblasts (RS) are erythroid precursors with abnormal perinuclear mitochondrial iron accumulation. Two myeloid neoplasms defined by the presence of RS, include refractory anemia with ring sideroblasts (RARS), now classified under myelodysplastic syndromes with RS (MDS-RS) and RARS with thrombocytosis (RARS-T); now called myelodysplastic/myeloproliferative neoplasm with RS and thrombocytosis (MDS/MPN-RS-T).

Diagnosis: MDS-RS is a lower-risk MDS, with single or multilineage dysplasia (SLD/MLD), <5% bone marrow (BM) blasts and ≥ 15% BM RS (≥5% in the presence of SF3B1 mutations). Read More

Pediatr Blood Cancer 2019 04 26;66(4):e27591. Epub 2018 Dec 26.

Department of Paediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.

Background: Sideroblastic anemia represents a heterogeneous group of inherited or acquired diseases with disrupted erythroblast iron utilization, ineffective erythropoiesis, and variable systemic iron overload. In a cohort of 421 patients with multisystem mitochondrial diseases, refractory anemia was found in 8 children.

Results: Five children had sideroblastic anemia with increased numbers of ring sideroblasts >15%. Read More

Clin Lymphoma Myeloma Leuk 2019 01 23;19(1):1-8. Epub 2018 Nov 23.

H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL. Electronic address:

Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are hybrid group of chronic myeloid neoplasms combining features of both MDS and MPN. The World Health Organization classification coined this group designation in 2008 to include chronic myelomonocytic leukemia, atypical chronic myeloid leukemia, juvenile myelomoncoytic leukemia, refractory anemia with ring sideroblasts and thrombocytosis as a provisional entity, and MDS/MPN unclassified. In this review, we highlight the challenges in diagnosing this group of the diseases, summarize the updates in classification, and discuss recent evolving understanding of the genetic landscape. Read More

Oncol Lett 2018 Dec 26;16(6):7287-7294. Epub 2018 Sep 26.

Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Suzhou, Jiangsu 215006, P.R. China.

Previous studies on the pathogenesis of myelodysplastic syndrome (MDS) have identified multiple associated gene mutations, including mutations of tetmethylcytosinedioxygenase 2, isocitrate dehydrogenase [NADP(+)] 1 cytosolic, isocitrate dehydrogenase [NADP(+)] 2 mitochondrial and additional sex combs like 1 transcriptional regulator, all of which may be considered epigenetic regulators. Furthermore, mutations of RAS type GTPase family genes have been identified in 10-15% patients with MDS. The authors' previous study on the gene expression profile of cluster of differentiation 34 cells using microarray analysis identified elevated expression of RAP1GTPase activating protein 1 (Rap1GAP) in patients with MDS compared with that in non-malignant blood diseases (NM) control group. Read More

Int J Hematol 2018 Dec 23;108(6):598-606. Epub 2018 Oct 23.

Department of Hematology, Juntendo University School of Medicine, Tokyo, Japan.

Splicing factor gene mutations are found in 60-70% of patients with myelodysplastic syndromes (MDS). We investigated the effects of splicing factor gene mutations on the diagnosis, patient characteristics, and prognosis of MDS. A total of 106 patients with MDS were included. Read More

Haematologica 2019 03 4;104(3):497-504. Epub 2018 Oct 4.

Assistance Publique-Hôpitaux de Paris (AP-HP), Service d'Hématologie Biologique, Hôpitaux Universitaires Paris Centre, Institut Cochin, Université Paris Descartes.

Erythropoiesis-stimulating agents are generally the first line of treatment of anemia in patients with lower-risk myelodysplastic syndrome. We prospectively investigated the predictive value of somatic mutations, and biomarkers of ineffective erythropoiesis including the flow cytometry RED score, serum growth-differentiation factor-15, and hepcidin levels. Inclusion criteria were no prior treatment with erythropoiesis-stimulating agents, low- or intermediate-1-risk myelodysplastic syndrome according to the International Prognostic Scoring System, and a hemoglobin level <10 g/dL. Read More

Mutat Res 2018 Jul - Sep;777:52-63. Epub 2018 Jun 22.

Univ. Rennes, CNRS, IGDR (Institut de génétique et développement de Rennes) - UMR 6290, F- 35000 Rennes, France. Electronic address:

Anemia is defined by a deficiency of hemoglobin, an iron-rich protein that binds oxygen in the blood. It can be due to multiple causes, either acquired or genetic. Alterations of genes involved in iron metabolism may be responsible, usually at a young age, for rare forms of chronic and often severe congenital anemia. Read More

J Hematol Oncol 2018 02 12;11(1):19. Epub 2018 Feb 12.

Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, Henan, People's Republic of China.

Background: SF3B1 is a core component of splicing machinery. Mutations in SF3B1 are frequently found in myelodysplastic syndromes (MDS), particularly in patients with refractory anemia with ringed sideroblasts (RARS), characterized by isolated anemia. SF3B1 mutations have been implicated in the pathophysiology of RARS; however, the physiological function of SF3B1 in erythropoiesis remains unknown. Read More

Zhonghua Xue Ye Xue Za Zhi 2017 Dec;38(12):1012-1016

Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC, The State Key Laboratory of Experimental Hematology, Tianjin 300020, China.

To study the characteristics of gene mutations in Chinese myelodysplastic syndromes (MDS) patients. A total of 511 Chinese patients with MDS performed 112-gene targeted sequencing were retrospectively analyzed. Eighty-three distinct mutant genes were found in 511 patients with MDS. Read More

Am J Med Genet A 2018 03 13;176(3):687-691. Epub 2018 Jan 13.

Department of Medical Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

Patients with isolated methylmalonic acidemia (MMA) may present with a wide range of hematological complications including anemia, leukopenia, thrombocytopenia, and pancytopenia. However, there are very limited data on the development of hemophagocytosis or myelodysplasia in these patients. We report three patients with isolated MUT related MMA who presented with severe refractory pancytopenia during acute illness. Read More

Tidsskr Nor Laegeforen 2017 11 13;137(21). Epub 2017 Nov 13.

Klin Padiatr 2017 Nov 13;229(6):329-334. Epub 2017 Nov 13.

Faculty of Medicine, Department of Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg.

Individuals with Fanconi anemia (FA) have a high risk of developing myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), yet the secondary somatic mutations lending to these malignancies remain to be further elucidated. We employed a next-generation sequencing myeloid neoplasia gene panel to determine the mutational spectrum of FA-related MDS/AML. Ten of 16 patients showed missense, nonsense, insertion or duplication mutations in 13 genes. Read More

Blood Res 2017 Mar 27;52(1). Epub 2017 Mar 27.

Department of Pathology, IMS &SUM Hospital, Bhubaneswar, India.

Am J Hematol 2017 Mar;92(3):297-310

Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.

Disease Overview: Ring sideroblasts (RS) are erythroid precursors with abnormal perinuclear mitochondrial iron accumulation. Two myeloid neoplasms defined by the presence of RS, include refractory anemia with ring sideroblasts (RARS), now classified under myelodysplastic syndromes with RS (MDS-RS) and RARS with thrombocytosis (RARS-T); now called myelodysplastic/myeloproliferative neoplasm with RS and thrombocytosis (MDS/MPN-RS-T).

Diagnosis: MDS-RS is a lower risk MDS, with single or multilineage dysplasia (SLD/MLD), <5% bone marrow (BM) blasts and ≥15% BM RS (≥5% in the presence of SF3B1 mutations). Read More

Hematol Rep 2016 Nov 2;8(4):6592. Epub 2016 Nov 2.

Department of Hematology/Oncology, Medical College of Georgia, Augusta University , Augusta, GA, USA.

Refractory anemia with ring sideroblasts associated with marked thrombocytosis (RARS-T) is a hematologic malignancy that often results in transfusion dependency and a hypercoagulable state. This rare disease currently lacks formal guidelines for treatment; however, various case reports have demonstrated efficacy in the use of lenalidomide. This immunomodulatory drug has shown promise in patients with 5q deletions, with reports of achieving transfusion independence and normalization of platelet counts. Read More

Cancer Biol Med 2016 Sep;13(3):360-372

Malignant Hematology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.

The myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) are a unique group of hematologic malignancies characterized by concomitant myelodysplastic and myeloproliferative features. According to the 2008 WHO classification, the category includes atypical chronic myeloid leukemia (aCML), chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), MDS/MPN-unclassifiable (MDS/MPN-U), and the provisional entity refractory anemia with ring sideroblasts and thrombocytosis (RARS-T). Although diagnosis currently remains based on clinicopathologic features, the incorporation of next-generation platforms has allowed for the recent molecular characterization of these diseases which has revealed unique and complex mutational profiles that support their distinct biology and is anticipated to soon play an integral role in diagnosis, prognostication, and treatment. Read More

Leukemia 2016 11 1;30(11):2273-2275. Epub 2016 Aug 1.

Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.

Leuk Lymphoma 2017 07 24;58(7):1686-1693. Epub 2016 Oct 24.

a Department of Hematology , University Hospital La Fe , Valencia , Spain.

The incidence of SF3B1 mutations in patients with RARS is high. Recently, it has been shown that SF3B1 and DNMT3A mutations overlap more often than expected, although it is not clear how this could affect the disease. We studied SF3B1 and DNMT3A in 123 RARS patients: 101 out of 123 samples (82%) had somatic mutations in SF3B1, and 13 of them (13%) showed a co-mutation (SF3B1DNMT3A). Read More

Vnitr Lek Fall 2016;62(9):692-697

Introduction: Megaloblastic anemia (MA) represents a subtype of macrocytic anemia caused by impaired DNA synthesis, mostly due to folate and vitamin B12 deficiency. Its mildest forms lead to macrocytosis without concomitant anemia, but more severe forms to thrombocytopenia and/or leucopenia as well. In majority of the cases, the diagnosis of MA dose not represent a serious clinical problem, however, other causes of macrocytosis including myelodysplastic syndrome (MDS) must be excluded. Read More

Clin Lymphoma Myeloma Leuk 2016 11 12;16(11):607-609. Epub 2016 Aug 12.

Pathology and Laboratory Medicine, Departments of Pathology and Medicine, James P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY. Electronic address:

In comparison with the 2008 World Health Organization "Blue Book" on hematopoietic neoplasms, a small number of changes have been made in the classification. In the lower-risk patients, Refractory Cytopenias with Multilineage Dysplasia and Ring Sideroblasts (RCMD-RS) has been separated from RCMD to recognize the importance of the SF3B1 mutation. Often there has been confusion as to the degree of morphologic dysplasia and/or cytopenias to define some of the lower-risk subtypes. Read More

Curr Hematol Malig Rep 2016 12;11(6):425-433

H. Lee Moffitt Cancer Center and Research Institute, Malignant Hematology, Tampa, FL, USA.

According to the recently published 2016 World Health Organization (WHO) classification of myeloid malignancies, myelodysplastic/myeloproliferative neoplasms (MDS/MPN) include atypical chronic myeloid leukemia (aCML), MDS/MPN-unclassifiable (MDS/MPN-U), chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), and MDS/MPN ring sideroblasts with thrombocytosis (MDS/MPN-RS-T). MDS/MPN-RS-T was previously a provisional category known as refractory anemia with ring sideroblasts with thrombocytosis (RARS-T) which has now attained a distinct designation in the 2016 WHO classification. In this review, we focus on biology and management of aCML, MDS/MPN-U, and MDS/MPN-RS-T. Read More

Cancer Cell 2016 09;30(3):404-417

Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address:

More than 80% of patients with the refractory anemia with ring sideroblasts subtype of myelodysplastic syndrome (MDS) have mutations in Splicing Factor 3B, Subunit 1 (SF3B1). We generated a conditional knockin mouse model of the most common SF3B1 mutation, Sf3b1(K700E). Sf3b1(K700E) mice develop macrocytic anemia due to a terminal erythroid maturation defect, erythroid dysplasia, and long-term hematopoietic stem cell (LT-HSC) expansion. Read More

Br J Haematol 2016 09 8;174(6):847-58. Epub 2016 Jul 8.

Department of Molecular Medicine, University of Pavia, Pavia, Italy.

Myeloid neoplasms with ring sideroblasts are currently categorized within the myelodysplastic syndromes (MDS) or myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in the World Health Organization classification. Recent findings have identified that the presence of ring sideroblasts in these disorders has a unique molecular basis, i.e. Read More

Am J Hematol 2016 Oct 4;91(10):1056. Epub 2016 Jul 4.

Department of Haematology, St Mary's Hospital and Centre for Haematology, St Mary's Hospital Campus of Imperial College Faculty of Medicine, St Mary's Hospital, London, United Kingdom.

Cancer Epidemiol 2016 06 16;42:186-98. Epub 2016 Apr 16.

Queens Centre for Oncology, Castle Hill Hospital, HU16 5JQ, UK.

Background: Population-based information on cancer incidence, prevalence and outcome are required to inform clinical practice and research; but contemporary data are lacking for many myeloid malignancy subtypes.

Methods: Set within a socio-demographically representative UK population of ∼4 million, myeloid malignancy data (N=5231 diagnoses) are from an established patient cohort. Information on incidence, survival (relative & overall), transformation/progression, and prevalence is presented for >20 subtypes. Read More

Leuk Lymphoma 2016 12 13;57(12):2905-2907. Epub 2016 Apr 13.

b Department of Medicine, Division of Hematology/Oncology , University of Wisconsin , Madison , WI , USA.

Blood Cancer J 2016 Mar 11;6:e405. Epub 2016 Mar 11.

Division of Hematopathology, Mayo Clinic, Rochester, MN, USA.

Am J Hematol 2016 May 4;91(5):492-8. Epub 2016 Apr 4.

Division of Hematology, Mayo Clinic, Rochester, Minnesota.

Refractory anemia with ring sideroblasts and thrombocytosis (RARS-T) shares overlapping features of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN). RARS-T is characterized by SF3B1 and JAK2 mutations and prognosis is considered to be better than MDS but not as good as MPN. The objective of the study was to identify predictors of survival in RARS-T. Read More

Bull Acad Natl Med 2016 Feb;200(2):335-347

Microcytic anemia is often due to disorder of globin genes. Here, we focus on rare monogenic microcytic anemias, We describe the diferent congenital forms that are due to mutations in genes implicated in iron homeostasis, the heme biosynthesis pathway, the cluster Fe-S biosynthesis pathway andmitochondrial proteins biosynthesis pathway. Among rare congenital microcytic anemias, most frequent forms are non syndromic sideroblastic anemias and iron refractory iron deficiency anemias (IRIDA). Read More

Hematology Am Soc Hematol Educ Program 2015 ;2015:294-8

Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA.

A revision to the 4th edition of the WHO Classification of myelodysplastic syndromes (MDSs), originally published in 2008, is expected in mid-2016. Based on recommendations of a Clinical Advisory Committee, the revision will aim to incorporate new discoveries in MDS that impact existing disease categories. Although the basic diagnostic principles of the WHO classification remain unchanged, several changes to the classification are proposed. Read More

Hematology Am Soc Hematol Educ Program 2015 ;2015:19-25

Department of Hematology Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia; and Department of Molecular Medicine, University of Pavia Medical School, Pavia, Italy.

The sideroblastic anemias are a heterogeneous group of inherited and acquired disorders characterized by the presence of ring sideroblasts in the bone marrow. X-linked sideroblastic anemia (XLSA) is caused by germline mutations in ALAS2. Hemizygous males have a hypochromic microcytic anemia, which is generally mild to moderate and is caused by defective heme synthesis and ineffective erythropoiesis. Read More

Rheumatology (Oxford) 2016 Feb 8;55(2):291-300. Epub 2015 Sep 8.

AP-HP, Hôpital Saint Antoine, service de medicine interne and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris,

Objective: We describe myelodysplastic syndrome (MDS)-associated systemic inflammatory and autoimmune diseases (SIADs), their treatments and outcomes and the impact of SIADs on overall survival in a French multicentre retrospective study.

Methods: In this study, 123 patients with MDS and SIADs were analysed.

Results: Mean age was 70 years (s. Read More

Haematologica 2015 Sep;100(9):1117-30

H. Lee Moffitt Cancer Center, Tampa, FL, USA.

In the 2008 WHO classification, chronic myeloid malignancies that share both myelodysplastic and myeloproliferative features define the myelodysplastic/myeloproliferative group, which includes chronic myelomonocytic leukemia, juvenile myelomonocytic leukemia, atypical chronic myeloid leukemia, refractory anemia with ring sideroblasts and thrombocytosis, and myelodysplastic/myeloproliferative unclassified. With the notable exception of refractory anemia with ring sideroblasts and thrombocytosis, there is much overlap among the various subtypes at the molecular and clinical levels, and a better definition of these entities, an understanding of their biology and an identification of subtype-specific molecular or cellular markers are needed. To address some of these challenges, a panel comprised of laboratory and clinical experts in myelodysplastic/myeloproliferative was established, and four independent academic MDS/MPN workshops were held on: 9(th) March 2013, in Miami, Florida, USA; 6(th) December 2013, in New Orleans, Louisiana, USA; 13(th) June 2014 in Milan, Italy; and 5(th) December 2014 in San Francisco, USA. Read More

Br J Haematol 2015 Nov 10;171(4):478-90. Epub 2015 Aug 10.

Karolinska Institutet, Department of Medicine (Huddinge), Centre for Hematology and Regenerative Medicine, Stockholm, Sweden.

Refractory anaemia with ring sideroblasts (RARS) is distinguished by hyperplastic inefficient erythropoiesis, aberrant mitochondrial ferritin accumulation and anaemia. Heterozygous mutations in the spliceosome gene SF3B1 are found in a majority of RARS cases. To explore the link between SF3B1 mutations and anaemia, we studied mutated RARS CD34(+) marrow cells with regard to transcriptome sequencing, splice patterns and mutational allele burden during erythroid differentiation. Read More

Ann Hematol 2015 Oct 25;94(10):1639-43. Epub 2015 Jul 25.

RE Kavetsky Institute of Experimental Pathology, Oncology & Radiobiology of the National Academy of Sciences of Ukraine, Vasylkivska 45, 03022, Kyiv, Ukraine,

The studies of the recent decades posed the question of the association between radiation exposure and myelodysplastic syndromes (MDS). This association has been proved in secondary MDS originating upon exposure to chemotherapeutics and/or radiation therapy. The long-term study in Japanese atomic (A)-bomb survivors demonstrated the significant linear dose-response for MDS confirming the link between radiation exposure and this form of hematopoietic malignancies. Read More

Am J Hematol 2015 Aug 28;90(8):E148-9. Epub 2015 May 28.

Department of Hematology, San Bortolo Hospital, Vicenza, Italy.

Blood 2015 Jul 8;126(2):233-41. Epub 2015 May 8.

Center for Hematology and Regenerative Medicine, Karolinska University Hospital, Stockholm, Sweden;

Refractory anemia with ring sideroblasts (RARS) is a myelodysplastic syndrome (MDS) characterized by isolated erythroid dysplasia and 15% or more bone marrow ring sideroblasts. Ring sideroblasts are found also in other MDS subtypes, such as refractory cytopenia with multilineage dysplasia and ring sideroblasts (RCMD-RS). A high prevalence of somatic mutations of SF3B1 was reported in these conditions. Read More

PLoS One 2015 8;10(5):e0126555. Epub 2015 May 8.

IBMCC, Centro de Investigación del Cáncer (CIC), Universidad de Salamanca-CSIC, Salamanca, Spain; IBSAL, Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain; Servicio de Hematología, Hospital Universitario de Salamanca, Salamanca, Spain.

The presence of SF3B1 gene mutations is a hallmark of refractory anemia with ring sideroblasts (RARS). However, the mechanisms responsible for iron accumulation that characterize the Myelodysplastic Syndrome with ring sideroblasts (MDS-RS) are not completely understood. In order to gain insight in the molecular basis of MDS-RS, an integrative study of the expression and mutational status of genes related to iron and mitochondrial metabolism was carried out. Read More

Leuk Lymphoma 2016 25;57(1):212-5. Epub 2015 Jun 25.

b Department of Laboratory Medicine , Cleveland Clinic , Cleveland , OH , USA.

Zhonghua Xue Ye Xue Za Zhi 2015 Apr;36(4):297-301

MDS Center, 1st Affiliated Hospital College of Medicine, Zhejiang University, Hangzhou 310003, China.

Objective: To investigate the relationship between cytogenetic markers with World Health Organization (WHO) classification, disease progress and prognosis in cases with primary myelodysplastic syndromes (MDS).

Methods: 298 patients with de novo MDS from the first affiliated hospital of medical school, Zhejiang University were enrolled in the retrospective analysis of WHO classification, karyotype, and prognosis. Follow-up study was also conducted. Read More

Am J Hematol 2015 Jun;90(6):549-59

Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.

Disease Overview: Ring sideroblasts (RS) are erythroid precursors with abnormal perinuclear mitochondrial iron accumulation. Two myeloid neoplasms defined by the presence of RS, include refractory anemia with ring sideroblasts (RARS) and RARS with thrombocytosis (RARS-T).

Diagnosis: RARS is a lower risk myelodysplastic syndrome (MDS) with dysplasia limited to the erythroid lineage, <5% bone marrow (BM) blasts and ≥15% BM RS. Read More

Haematologica 2015 Apr 19;100(4):e125-7. Epub 2014 Dec 19.

MLL Munich Leukemia Laboratory, Munich, Germany

Leukemia 2015 May 27;29(5):1092-103. Epub 2014 Nov 27.

LLR Molecular Haematology Unit, NDCLS, RDM, University of Oxford, Oxford, UK.

The splicing factor SF3B1 is the most commonly mutated gene in the myelodysplastic syndrome (MDS), particularly in patients with refractory anemia with ring sideroblasts (RARS). We investigated the functional effects of SF3B1 disruption in myeloid cell lines: SF3B1 knockdown resulted in growth inhibition, cell cycle arrest and impaired erythroid differentiation and deregulation of many genes and pathways, including cell cycle regulation and RNA processing. MDS is a disorder of the hematopoietic stem cell and we thus studied the transcriptome of CD34(+) cells from MDS patients with SF3B1 mutations using RNA sequencing. Read More

Ann Hematol 2015 Apr 13;94(4):565-73. Epub 2014 Nov 13.

Department of Hematology, Hospital General Universitario Gregorio Marañon, C/ Doctor Esquerdo 46, 28007, Madrid, Spain,

Previous studies have shown the reproducibility of the 2008 World Health Organization (WHO) classification in myelodysplastic syndromes (MDS), especially when multilineage dysplasia or excess of blasts are present. However, there are few data regarding the reproducibility of MDS with unilineage dysplasia. The revised International Prognostic Scoring System R-IPSS described two new morphological categories, distinguishing bone marrow (BM) blast cell count between 0-2 % and >2- < 5 %. Read More

Int J Hematol 2014 Dec 17;100(6):521-2. Epub 2014 Sep 17.

Department of Haematology, University Hospital of Amiens, Amiens, France.

Int J Hematol 2015 Mar 12;101(3):229-42. Epub 2014 Sep 12.

Haematology Research Laboratory, Biomedical Research Foundation, Academy of Athens, Athens, Greece.

According to the 2008 WHO classification, the category of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) includes atypical chronic myeloid leukaemia (aCML), chronic myelomonocytic leukaemia (CMML), MDS/MPN-unclassifiable (MDS/MPN-U), juvenile myelomonocytic leukaemia (JMML) and a "provisional" entity, refractory anaemia with ring sideroblasts and thrombocytosis (RARS-T). The remarkable progress in our understanding of the somatic pathogenesis of MDS/MPN has made it clear that there is considerable overlap among these diseases at the molecular level, as well as layers of unexpected complexity. Deregulation of signalling plays an important role in many cases, and is clearly linked to more highly proliferative disease. Read More

Curr Hematol Malig Rep 2014 Dec;9(4):400-6

Leukemia Program, Cleveland Clinic Taussig Cancer Institute, Desk R35, 9500 Euclid Avenue, Cleveland, OH, 44195, USA,

Patients with the myelodysplastic syndromes/myeloproliferative neoplasm (MDS/MPN) overlap, including chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (aCML), MDS/MPN-unclassifiable (MDS/MPN-U), and refractory anemia with ring sideroblasts associated with marked thrombocytosis (RARS-T), often present with findings of both dysplasia and marrow proliferation, occupying the border region of two seemingly divergent camps. Historically, these disorders which have been lumped with either MDS or MPN have represented a minority, or been excluded all together, from the development of prognostic models and clinical trials. Therefore, Food and Drug Administration approved therapies specifically for overlap subtypes are lacking. Read More