Myelodysplastic Syndromes (MDS)

Myelodysplastic syndromes (MDS) are a group of clonal stem cell disorders caused by ineffective hematopoiesis due to disordered development and dysmaturation of blood cells in the bone marrow.1-3 MDS affects 1 or more of the 3 blood cell lines (erythroid, megakaryocytic, and neutrophilic).1 

Clinical features of MDS include dysplasia, 1 or more peripheral blood cytopenias (anemia, neutropenia, and/or thrombocytopenia), the presence of blast cells in the bone marrow and/or peripheral blood, and a higher risk of progression to acute myeloid leukemia (AML).1,3

Earliest Mention of MDS in the Literature

In 1900, Wilhelm von Leube, a German pathologist and physician, first described a case of “leukanemia” in which the patient demonstrated rapidly progressing, severe, pernicious anemia that preceded the development of overt leukemia.3-5 Subsequent cases characterized by cytopenia, increased marrow blasts, problems with marrow precursor maturation, and a high likelihood of transformation to AML followed this initial description.3

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Connections Made During the 1940s and 1950s

During the 1940s and 1950s, scientists made the connection between bone marrow failure and the development of leukemia. In 1942, Paul Chevallier, a hematologist from Paris, suggested using the term “odo-leucoses” to indicate that bone marrow failure syndromes are “pathways” or “roads” leading to leukemia.6

In 1949, James L. Hamilton-Paterson, a British pathologist and physician, described cases of preleukemic anemia and suggested that the dyshematopoietic agent causing the anemia also caused the leukemia. He also mentioned that agents like thorium, y-rays, and benzole can lead to direct poisoning of the bone marrow leading to anemia, followed by polycythaemia vera with abnormalities of the hematopoietic system.6,7

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First Classifications of MDS

The French-American-British (FAB) Cooperative Group held a series of meetings from 1974 to 1975 to refine acute leukemia classifications and nomenclature. This international group consisted of 7 hematologists: John M. Bennett, Daniel Catovsky, Marie-Therese Daniel, G. Flandrin, D.A.G. Galton, H.R. Gralnick, and C. Sultan.6 

After performing case reviews, the FAB Cooperative Group came up with the term “dysmyelopoietic syndromes” for MDS cases and categorized these conditions as separate from AML. They published their proposals to establish a more uniform classification system for acute leukemias and related conditions, such as MDS, in August 1976.6,8

The FAB Cooperative Group further refined this classification system in 1982, changing the term from “dysmyelopoietic syndromes” to the currently used modern term, “myelodysplastic syndromes.”6,9 They described 5 subcategories of MDS and the quantitative and qualitative histological abnormalities required for the diagnosis of each subtype, including6,9:

  • Refractory anemia (RA) with less than 5% blast cells in the bone marrow and less than 1% blasts in the peripheral blood
  • RA with ring sideroblasts with less than 5% blast cells in the bone marrow and less than 1% blasts in the peripheral blood
  • RA with excess blasts (RAEB) with 5% to 20% blasts in the bone marrow and less than 5% blasts in the peripheral blood
  • Chronic myelomonocytic leukemia (CMML)
  • RAEB in transformation, which is considered whenever there is greater than 5% blasts in the peripheral blood, 20% to 30% blasts in the bone marrow, and the presence of Auer rods in granulocyte precursors in the bone marrow or peripheral blood

In 1982, the FAB Cooperative Group indicated that anything over 30% of bone marrow blasts supported a diagnosis of AML.9 

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Advancements in Diagnostic Testing and Prognosis of MDS

After the 1982 FAB classification for MDS was published, new diagnostic techniques in cytogenetics and molecular genetics enabled researchers to identify correlations between genetics and the various MDS subtypes and further understand etiological factors driving the development of MDS.3,6 

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During the 1990s, chromosome analysis in particular further guided, clarified, and refined diagnosis, prognosis, treatments, and definitions for MDS subtypes.3,6 Since the first FAB proposal, researchers have published over 20,000 scientific articles exploring various aspects of MDS, such as treatments and prognosis.6

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World Health Organization Classifications of MDS

The World Health Organization (WHO) first published its classification system for MDS diagnosis in 2002,10 followed by subsequent revisions in 200811 and 2016.12 The most recent WHO iteration of the most updated criteria and classification of MDS subtypes was published in 2022.13 

Read more about MDS guidelines


  1. Dotson JL, Lebowicz Y. Myelodysplastic syndrome. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2023. Updated July 18, 2022. Accessed June 20, 2023. 
  2. Myelodysplastic syndromes. National Organization for Rare Disorders (NORD). Updated July 24, 2020. Accessed June 20, 2023.
  3. Hellström-Lindberg E. Myelodysplastic syndromes: an historical perspective. Hematology Am Soc Hematol Educ Program. 2008;2008(1):42. doi:10.1182/asheducation-2008.1.42
  4. Zini G. Diagnostics and prognostication of myelodysplastic syndromes. Ann Lab Med. 2017;37(6):465-474. doi:10.3343/alm.2017.37.6.465
  5. von Leube W. Rapid verlaufende schwere Anämie mit gleichzeitiger leukämischer Veränderung del Blutbildes [Rapidly progressing severe anemia with simultaneous leukemic changes in the blood picture]. Klin Wochenschr. 1900;37:85. German.
  6. Steensma DP. Historical perspectives on myelodysplastic syndromes. Leuk Res. 2012;36(12):1441-1452. doi:10.1016/j.leukres.2012.08.007
  7. Hamilton-Paterson JL. Pre leukaemic anaemia. Acta Haematol. 1949;2(5):309-316. doi:10.1159/000203474
  8. Bennett JM, Catovsky D, Daniel MT, et al. Proposals for the classification of the acute leukaemias French-American-British (FAB) Co-operative Group. Br J Haematol. 1976;33(4):451-458. doi:10.1111/j.1365-2141.1976.tb03563.x
  9. Bennett JM, Catovsky D, Daniel MT, et al. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol. 1982;51(2):189-199. doi:10.1111/j.1365-2141.1982.tb02771.x
  10. Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood. 2002;100(7):2292-2302. doi:10.1182/blood-2002-04-1199
  11. Vardiman JW, Thiele J, Arber DA, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114(5):937-951. doi:10.1182/blood-2009-03-209262
  12. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-2405. doi:10.1182/blood-2016-03-643544
  13. Khoury JD, Solary E, Abla O, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: myeloid and histiocytic/dendritic neoplasms. Leukemia. 2022;36(7):1703-1719. doi:10.1038/s41375-022-01613-1

Reviewed by Debjyoti Talukdar, MD, on 6/23/2023.