Myelodysplastic Syndromes (MDS)

Myelodysplastic syndromes (MDS) are a group of rare hematologic neoplasms characterized by the inability of affected hematopoietic stem cells in the bone marrow to produce mature, healthy blood cells. These syndromes can affect any of the 3 major blood cell lineages—the erythroid, neutrophilic, and megakaryocytic lines.¹

If MDS is suspected, an examination of the blood and bone marrow is required to confirm the diagnosis, determine the MDS subtype, and rule out other possible conditions.²

Laboratory Testing for MDS

Basic Laboratory Testing

A complete blood count (CBC) tests for the number of erythrocytes, leukocytes, and platelets in a blood sample. A CBC with differential examines the number of different types of leukocytes in more depth.² The most common findings for individuals with MDS include²:

• Low red blood cell count (anemia)
• Low white blood cell count (leukopenia)
• Low platelet levels (thrombocytopenia).

Specific blood tests and panels checking for iron, folate, or vitamin B12 deficiencies may rule out other possible causes of anemia that make a diagnosis of MDS less probable.²

Peripheral Blood Smear

A peripheral blood smear may be ordered alongside a CBC or when abnormal results are returned. In this test, a laboratory specialist spreads some of the blood sample on a microscope slide to examine the blood.² Some people with specific subtypes of MDS may have myeloblasts or blasts (immature blood cells that are usually only found in the bone marrow) circulating in the peripheral blood. Blasts in the peripheral blood are usually a sign of bone marrow disorders.²

Other features that pathologists might look for when examining the peripheral blood sample include abnormalities in blood cell size, shape, and other features.² 

Read more about MDS diagnosis

Bone Marrow Aspiration and Biopsy for MDS

Bone marrow aspiration and biopsy, usually performed on the posterior pelvic bone, are critical procedures required for an official MDS diagnosis. Aspiration involves sampling bone marrow fluid using a syringe, while biopsy involves obtaining a small sample of bone and marrow tissue.² 

Histological Examination

Specialists examine the bone marrow and blood samples under a microscope, looking at the size, shape, and percentage of blast cells. To confirm a diagnosis of MDS, these samples must demonstrate less than 20% blasts in the bone marrow and blood. Anything over 20% blasts denotes transformation to acute myeloid leukemia (AML).²

Microscopy may reveal signs of dysplasia in patients with MDS, including the following abnormal cell sizes, shapes, and features in the peripheral blood and bone marrow³:

• Erythrocytes demonstrate anisocytosis, poikilocytosis, polychromasia, hypochromasia, basophilic stippling, teardrop shapes, dimorphic features, or nucleated versions of erythroid precursors. Erythrocytes may also appear as megalocytes, ovalocytes, or fragmentocytes.
• Granulocytes in the peripheral blood demonstrate abnormal chromatin clumping, pseudo Pelger-Huet cells, hypodegranulation, and left shift.
• Platelets appear giant or demonstrate anisometry.
• Bone marrow cellularity is typically hypercellular and very rarely hypocellular.
• Erythropoiesis may show atypical mitoses, sideroblastosis, ring sideroblasts, nuclear bridges or budding, nonround nuclei, multinuclearity, megaloblastoid changes, karyorrhexis, and periodic acid-Schiff-positive red cell precursors.
• Granulocytopoiesis may show left shift, nuclear hypersegmentation or abnormal chromatin clumping, pseudo-Pelger cells, Auer rods or bodies, increased medullary blast count, increased or abnormal monocytes, hypodegranulation, or myeloperoxidase deficiency.
• Megakaryopoiesis may show multinuclearity with multiple isolated nuclei, dumbbell-shaped nuclei, hypersegmented nuclei, micromegakaryocytes, or mononuclear megakaryocytes.

Read more about MDS histology

Flow Cytometry and Immunocytochemistry Testing for MDS

During flow cytometry and immunocytochemical assessments, cell samples are treated with antibodies that bind only to specific proteins on cells. Microscopic evaluation confirms whether the antibodies stick to the cells, suggesting the presence or absence of these specific proteins. These studies differentiate between subtypes of MDS and rule out other differential diagnoses.² 

Read more about MDS differential diagnosis

Karyotyping Analysis for MDS

Karyotyping examines the chromosomes inside cells containing DNA. Chromosomal abnormalities occur commonly in patients with MDS.² Standard karyotype has the highest prognostic value.³

Cytogenetics

Cytogenetics looks at the number of chromosomes inside cells under a microscope. This evaluation detects deletions (del or -), additions (+), or translocations (t).² 

The most frequent karyotype abnormalities that present in around 50% of MDS cases include⁴:

• Deletions in chromosome 5, specifically del(5q)
• Deletions in chromosome 7, specifically del(7q)
• Trisomy 8
• Deletions in chromosome 11, specifically del(11q)
• Deletions in chromosome 12, specifically del(12p)
• Deletions in chromosome 17, specifically del(17p)
• Deletions in chromosome 20, specifically del(20q)
• Additions in chromosome 21, specifically +21q.

Individuals with 3 or more chromosomal changes, or complex karyotypes, have a poorer prognosis than those with del(5q) subtypes.² 

Clonal chromosomal abnormalities occur in 30% to 80% of patients with MDS. In the remaining 20% to 70% of patients, submicroscopic changes, such as microdeletions, amplifications, point mutations, epigenetic changes, or copy number neutral loss, may occur.³ 

Read more about MDS prognosis

Fluorescence In Situ Hybridization

Fluorescence in situ hybridization (FISH) examines DNA more closely using fluorescent dyes that attach to specific changes in genes or chromosomes.² The MDS panel for FISH examines 5 genes and variants, including PTPRT, EGR1, MECOM, KMT2A, and MYBL2, as well as 5 chromosomal regions and specific deletions, including chromosome 7 monosomy, trisomy 8, del(5q), del(7q), and del(20q).⁵

Polymerase Chain Reaction Testing

Polymerase chain reaction (PCR) testing identifies chromosomal changes that are difficult to observe under a microscope, along with a small number of abnormal cells in a sample.²

Genetic Mutation Analysis for MDS

Gene mutations, whether somatic or germline, contribute to the development of some MDS subtypes.⁴ Whole-genome sequencing, next-generation sequencing, whole-exome sequencing, and targeted gene panel testing can identify abnormal genetic variants that might be associated with MDS.⁶

In addition to isolated chromosome 5q deletion, other genetic tests may look for biallelic TP53 inactivation and SF3B1 mutations to rule out these specific subtypes of MDS with defining genetic associations.^7,8 

Read more about MDS genetics

References 

1. Myelodysplastic syndromes treatment (PDQ® version)–patient version. National Cancer Institute. Updated March 31, 2023. Accessed June 15, 2023.
2. Tests for myelodysplastic syndromes. American Cancer Society. Updated January 22, 2018. Accessed June 15, 2023.
3. Fenaux P, Haase D, Santini V, Sanz GF, Platzbecker U, Mey U; ESMO Guidelines Committee. Myelodysplastic syndromes: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2021;32(2):142-156. doi:10.1016/j.annonc.2020.11.002
4. Saygin C, Godley LA. Genetics of myelodysplastic syndromes. Cancers (Basel). 2021;13(14):3380. doi:10.3390/cancers13143380
5. FISH, MDS panel. Genetic Testing Registry (GTR). Updated August 11, 2020. Accessed June 15, 2023.
6. Duncavage EJ, Bagg A, Hasserjian RP, et al. Genomic profiling for clinical decision making in myeloid neoplasms and acute leukemia. Blood. 2022;140(21):2228-2247. doi:10.1182/blood.2022015853
7. 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
8. Huber S, Haferlach T, Meggendorfer M, et al. SF3B1 mutated MDS: blast count, genetic co-abnormalities and their impact on classification and prognosis. Leukemia. 2022;36(12):2894-2902. doi:10.1038/s41375-022-01728-5

Reviewed by Harshi Dhingra, MD, on 6/14/2023.

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Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT

Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT is a freelance medical writer and Doctor of Physical Therapy from Maryland. She has expertise in the therapeutic areas of orthopedics, neurology, chronic pain, gastrointestinal dysfunctions, and rare diseases especially Ehlers Danlos Syndrome.