Myelodysplastic Syndromes (MDS) Overview

MDS refers to a heterogeneous group of clonal hematopoietic stem cell (HSC) disorders, resulting from acquired genetic or epigenetic aberrations. They are collectively characterized by bone marrow dysfunction, dysplasia, peripheral blood cytopenias, ineffective hematopoiesis, and reduced genomic stability.1-5 According to the World Health Organization (WHO), MDS is neoplastic and thus is classified as cancer.6 Furthermore, development of acute myeloid leukemia (AML) is also a significant risk in MDS, with 25% to 30% of patients progressing to AML.7,8

Patients with MDS experience significant cytopenias.8,9

  • Anemia is the most common cytopenia, affecting approximately 90% of patients at the time of MDS diagnosis7
  • Neutropenia is observed in approximately 50% of patients10
  • Thrombocytopenia occurs in approximately 40% of patients9

Because MDS share several characteristics and symptoms, such as cytopenias, with many other disorders, it is important to differentiate MDS from pre-MDS disorders and other syndromes.11,12

MDS may be de novo (also called primary) or treatment-related (t-MDS, also called secondary).4,13

  • t-MDS can occur as a late complication after receiving radiotherapy, chemotherapy, or immunosuppressive therapy14
  • Two types of t-MDS/AML are recognized, depending on the causative therapeutic exposure: an alkylating agent/radiation-related type and a topoisomerase II inhibitor-related type15

There are several differences between de novo MDS and t-MDS. Characteristics that may differ include:

Characteristic De Novo MDS t-MDS
Percentage of MDS patients diagnosed/year 85%-95%8 10%-15%16
Chromosomal instabilities with deletions and translocations 40%-70%17 90%14
Karyotype Normal or complex16 Complex16
Mutations ~90% carry at least one somatic mutation18 TP53 may be mutated in ~40% of cases19

Learn more about the epidemiology of MDS.

Learn more about chromosomal, epigenetic, and mutational abnormalities in MDS.

References: 1. Varney ME, Melgar K, Niederkorn M, et al. Deconstructing innate immune signaling in myelodysplastic syndromes. Exp Hematol. 2015;43(8):587‐598. 2. Adès L, Itzykson R, Fenaux P. Myelodysplastic syndromes. Lancet. 2014;383(9936):2239‐2252. 3. Bejar R, Steensma DP. Recent developments in myelodysplastic syndromes. Blood. 2014;124(18):2793‐2803. 4. Foran JM, Shammo JM. Clinical presentation, diagnosis, and prognosis of myelodysplastic syndromes. Am J Med. 2012;125(suppl 7):S6‐S13. 5. Steensma DP, Komrokji RS, Stone RM, et al. Disparity in perceptions of disease characteristics, treatment effectiveness, and factors influencing treatment adherence between physicians and patients with myelodysplastic syndromes. Cancer. 2014;120(11):1670‐1676. 6. Steensma DP, Bejar R, Jaiswal S, et al. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood. 2015;126(1):9‐16. 7. Zeidan AM, Shallis RM, Wang R, et al. Epidemiology of myelodysplastic syndromes: why characterizing the beast is a prerequisite to taming it. Blood Rev. 2019;34:1-15. 8. Steensma DP. Myelodysplastic syndromes: diagnosis and treatment. Mayo Clin Proc. 2015;90(7):969-983. 9. Greenberg PL, Tuechler H, Schanz J, et al. Revised International Prognostic Scoring System for myelodysplastic syndromes. Blood. 2012;120(12):2454-2465. 10. Toma A, Fenaux P, Dreyfus F, Cordonnier C. Infections in myelodysplastic syndromes. Haematologica. 2012;97(10):1459‐1470. 11. Valent P, Orazi A, Steensma DP, et al. Proposed minimal diagnostic criteria for myelodysplastic syndromes (MDS) and potential pre-MDS conditions. Oncotarget. 2017;8(43):73483-73500. 12. DeZern AE, Sekeres MA. The challenging world of cytopenias: distinguishing myelodysplastic syndromes from other disorders of marrow failure. Oncologist. 2014;19(7):735-745. 13. Samiev D, Bhatt VR, Armitage JD, et al. A primary care approach to myelodysplastic syndromes. Korean J Fam Med. 2014;35(3):111‐118. 14. Smith SM, Le Beau MM, Huo D, et al. Clinical-cytogenetic associations in 306 patients with therapy-related myelodysplasia and myeloid leukemia: the University of Chicago series. Blood. 2003;102(1):43-52. 15. Bhatia S. Therapy-related myelodysplasia and acute myeloid leukemia. Semin Oncol. 2013;40(6):666-675. 16. Pedersen-Bjergaard J, Christiansen DH, Andersen MK, Skovby F. Causality of myelodysplasia and acute myeloid leukemia and their genetic abnormalities. Leukemia. 2002;16(11):2177-2184. 17. List AF, Vardiman J, Issa JP, DeWitte TM. Myelodysplastic syndromes. Hematology Am Soc Hematol Educ Program. 2004;297-317. 18. Dao KT. Myelodysplastic syndromes: updates and nuances. Med Clin North Am. 2017;101(2):333-350. 19. Ok CY, Patel KP, Garcia-Manero G, et al. TP53 mutation characteristics in therapy-related myelodysplastic syndromes and acute myeloid leukemia is similar to de novo diseases. J Hematol Oncol. 2015;8:45.