Myelodysplastic Syndrome (MDS) with Single Lineage Dysplasia

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Primary Author(s)*

Xiaoli Du, Ph.D; Teresa Smolarek, Ph.D, FACMG

Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH, 45229, USA.

Cancer Category/Type

Myelodysplastic Syndrome

Cancer Sub-Classification / Subtype

Myelodysplastic Syndrome (MDS) with Single Lineage Dysplasia (SLD)

Definition / Description of Disease

Myelodysplastic syndrome (MDS) with single lineage dysplasia (SLD) is a category of MDS characterized by unexplained cytopenia or bi-cytopenia, ≥10% dysplastic cells in one myeloid lineage (red blood cells, white blood cells, or megakaryocytes), <5% of blasts in bone marrow and <1% blasts in peripheral blood, non-Auer rods, <15% ring sideroblasts in bone marrow or <5% if SF3B1 mutation is present [1]. MDS-SLD has a low risk of progression or transformation to acute myeloid leukemia and often follow a prolonged/ indolent clinical course. The presence of blasts in the peripheral blood excludes a diagnosis of MDS-SLD [2]. It is essential to exclude all possible non-clonal etiologies for the abnormalities such as: possible vitamin B12 or folic acid deficiency, copper deficiency, excessive zinc supplementation or paroxysmal nocturnal hemoglobinuria[3] [4]. Persistent cytopenia without morphological evidence of dysplasia or MDS-defining cytogenetic abnormalities should not be diagnosed as MDS-SLD. Without definitive morphological and/or cytogenetic evidence, it is recommended that the patient be observed for >=6 months before establishing the definitive diagnosis[1].

Synonyms / Terminology

Refractory cytopenia with unilineage dysplasia (RCUD), MDS-SLD

Epidemiology / Prevalence

MDS-SLD accounts for 7-20% of all cases of MDS[1] [5][6].

  • Occurs mainly in older patients
  • Median age is 65-70 years
  • No significant sex predilection

Clinical Features

The clinical phenotypes are often nonspecific and are generally related to the corresponding cytopenia. The recommended thresholds for cytopenia suggested by International Prognostic Scoring System (IPSS) [7]:

  • Hemoglobin concentration: <10 g/dL
  • Absolute neutrophil count: <1.8 x109/L AND
  • Platelet count: <100 x109/L

Sites of Involvement

Peripheral blood and bone marrow

Morphologic Features

The morphologic features of the peripheral blood and bone marrow are currently the gold standard for the diagnosis of MDS [1].

Categories   Morphologic Features

(≥10% of the nucleated erythroid precursors)

Nuclear budding, internuclear chromatin bridging, multinuclearity, megaloblastoid changes or karyorrhexis
Neutrophil dysplasia Small size, dense chromatin, nuclear hyposegmentation, granulation abnormalities
Megakaryocytic dysplasia

(≥10% dysplastic megakaryocytes)

Hypobated or bilobed nuclei, multiple separated nuclei, micromegakaryocytes


Same as the MDS immunophenotype; however, definitive morphological and/or cytogenetic findings can help establish the diagnosis. MDS-SLD with erythroid dysplasia shows aberrant immunophenotypic features of erythropoietic precursors[8]. Some of the cases show aberrant immunophenotypic features in the myelomonocytic compartment or in precursors[9].  

Chromosomal Rearrangements (Gene Fusions)


Characteristic Chromosomal Aberrations / Patterns

  • Del(20q), gain of chromosome 8, abnormalities with chromosome 5 and 7[10].

Genomic Gain/Loss/LOH

  • Nonspecific cytogenetic abnormalities have been observed in 50% of MDS-SLD cases.
  • Del(20q), gain of chromosome 8, abnormalities with chromosome 5 and 7[10] .

Gene Mutations (SNV/INDEL)

  • Somatic mutations have been identified in 60-70% of MDS-SLD cases.
  • Most frequent mutations: ASXL1, TET2, SF3B1, U2AF1, SRSF2[11][12][13].

Other Mutations


Epigenomics (Methylation)

DNA methylation genes DNMT3A, TET2, IDH1, and IDH2 are associated with MDS or excess blasts[14].

Genes and Main Pathways Involved

  • ASXL1: involved in chromatin remodeling
  • TET2:  involved in regulating transcription
  • SF3B1: involved in pre-mRNA splicing

Diagnostic Testing Methods

  • Quantification of dysplasia: Microscopy
  • Pathology: Immunophenotyping by flow cytometry
  • Genetics: Conventional karyotyping and sequencing

Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)

  • Diagnosis: Cytopenia or biocytopenia, ≥10% dysplastic cells in one myeloid lineage and exclude the non-clonal causes of dysplasia.
  • Prognosis: International Prognostic Scoring System (IPSS) was adopted and was accepted by the Myelodysplastic Syndrome Working Group[15]. The majority of patients with a diagnosis of MDS-SLD fall into the low-risk and intermediate-1–risk groups. Median survival of patients with MDS-SLD is approximately 66 months with the rate of progression to acute myeloid leukemia of 10% at 5 years[16] .
  • Therapeutic: The presence of SF3B1 somatic mutation is an unfavorable marker of response to Immunosuppressive Therapy[17]. MDS-SLD has been reported to be associated with autoimmune disorders such as autoimmune hemolytic anemia[18]. Steroids and immunosuppressive treatment (IST) remain the first-line treatment. However, due to the steroid dependence or relapse occurs in 50 to 70% of cases, accumulating evidence suggests that hypomethylating agents may be effective in treating these complications for the underlying MDS[18].

Familial Forms


Other Information



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  2. Gyan, Emmanuel; et al. (2015). "Refractory thrombocytopenia and neutropenia: a diagnostic challenge". Mediterranean Journal of Hematology and Infectious Diseases. 7 (1): e2015018. doi:10.4084/MJHID.2015.018. ISSN 2035-3006. PMC 4344166. PMID 25745545.
  3. Gregg, Xylina T.; et al. (2002-08-15). "Copper deficiency masquerading as myelodysplastic syndrome". Blood. 100 (4): 1493–1495. doi:10.1182/blood-2002-01-0256. ISSN 0006-4971. PMID 12149237.
  4. Irving, Julie A.; et al. (2003-07-22). "Element of caution: a case of reversible cytopenias associated with excessive zinc supplementation". CMAJ: Canadian Medical Association journal = journal de l'Association medicale canadienne. 169 (2): 129–131. ISSN 0820-3946. PMC 164980. PMID 12874162. Missing pipe in: |journal= (help)CS1 maint: PMC format (link)
  5. Della Porta, M. G.; et al. (2015-01). "Minimal morphological criteria for defining bone marrow dysplasia: a basis for clinical implementation of WHO classification of myelodysplastic syndromes". Leukemia. 29 (1): 66–75. doi:10.1038/leu.2014.161. ISSN 1476-5551. PMID 24935723. Check date values in: |date= (help)
  6. Germing, Ulrich; et al. (2012-06). "Evaluation of dysplasia through detailed cytomorphology in 3156 patients from the Düsseldorf Registry on myelodysplastic syndromes". Leukemia Research. 36 (6): 727–734. doi:10.1016/j.leukres.2012.02.014. ISSN 1873-5835. PMID 22421409. Check date values in: |date= (help)
  7. Greenberg, Peter L.; et al. (2012-09-20). "Revised international prognostic scoring system for myelodysplastic syndromes". Blood. 120 (12): 2454–2465. doi:10.1182/blood-2012-03-420489. ISSN 1528-0020. PMC 4425443. PMID 22740453.
  8. Porwit, A.; et al. (2014-09). "Revisiting guidelines for integration of flow cytometry results in the WHO classification of myelodysplastic syndromes-proposal from the International/European LeukemiaNet Working Group for Flow Cytometry in MDS". Leukemia. 28 (9): 1793–1798. doi:10.1038/leu.2014.191. ISSN 1476-5551. PMID 24919805. Check date values in: |date= (help)
  9. Kern, Wolfgang; et al. (2010-10-01). "Clinical utility of multiparameter flow cytometry in the diagnosis of 1013 patients with suspected myelodysplastic syndrome: correlation to cytomorphology, cytogenetics, and clinical data". Cancer. 116 (19): 4549–4563. doi:10.1002/cncr.25353. ISSN 0008-543X. PMID 20572043.
  10. 10.0 10.1 Braun, Thorsten; et al. (2011-07). "Characteristics and outcome of myelodysplastic syndromes (MDS) with isolated 20q deletion: a report on 62 cases". Leukemia Research. 35 (7): 863–867. doi:10.1016/j.leukres.2011.02.008. ISSN 1873-5835. PMID 21396711. Check date values in: |date= (help)
  11. Haferlach, T.; et al. (2014-02). "Landscape of genetic lesions in 944 patients with myelodysplastic syndromes". Leukemia. 28 (2): 241–247. doi:10.1038/leu.2013.336. ISSN 1476-5551. PMC 3918868. PMID 24220272. Check date values in: |date= (help)
  12. Wu, Lingyun; et al. (2016-04). "Genetic landscape of recurrent ASXL1, U2AF1, SF3B1, SRSF2, and EZH2 mutations in 304 Chinese patients with myelodysplastic syndromes". Tumour Biology: The Journal of the International Society for Oncodevelopmental Biology and Medicine. 37 (4): 4633–4640. doi:10.1007/s13277-015-4305-2. ISSN 1423-0380. PMID 26508027. Check date values in: |date= (help)
  13. Tefferi, Ayalew; et al. (2017-12). "Targeted next-generation sequencing in myelodysplastic syndromes and prognostic interaction between mutations and IPSS-R". American Journal of Hematology. 92 (12): 1311–1317. doi:10.1002/ajh.24901. ISSN 1096-8652. PMID 28875545. Check date values in: |date= (help)
  14. Malcovati, Luca; et al. (2014-08-28). "Driver somatic mutations identify distinct disease entities within myeloid neoplasms with myelodysplasia". Blood. 124 (9): 1513–1521. doi:10.1182/blood-2014-03-560227. ISSN 1528-0020. PMC 4148773. PMID 24970933.
  15. Greenberg, P.; et al. (1997-03-15). "International scoring system for evaluating prognosis in myelodysplastic syndromes". Blood. 89 (6): 2079–2088. ISSN 0006-4971. PMID 9058730.
  16. Maassen, Anna; et al. (2013-01). "Validation and proposals for a refinement of the WHO 2008 classification of myelodysplastic syndromes without excess of blasts". Leukemia Research. 37 (1): 64–70. doi:10.1016/j.leukres.2012.09.021. ISSN 1873-5835. PMID 23122806. Check date values in: |date= (help)
  17. Zhang, Qing; et al. (2020-06). "SF3B1 Mutations Negatively Predict for Response to Immunosuppressive Therapy in Myelodysplastic Syndromes". Clinical Lymphoma, Myeloma & Leukemia. 20 (6): 400–406.e2. doi:10.1016/j.clml.2019.12.023. ISSN 2152-2669. PMC 7771378 Check |pmc= value (help). PMID 32179032 Check |pmid= value (help). Check date values in: |date= (help)
  18. 18.0 18.1 Grignano, Eric; et al. (2018-11). "Autoimmune manifestations associated with myelodysplastic syndromes". Annals of Hematology. 97 (11): 2015–2023. doi:10.1007/s00277-018-3472-9. ISSN 1432-0584. PMID 30091023. Check date values in: |date= (help)


  1. Arber, Daniel A.; et al. (2016). "The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia". Blood. 127 (20): 2391–2405. doi:10.1182/blood-2016-03-643544. ISSN 1528-0020. PMID 27069254
  2. Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p129-171.


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