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PubMed This is a summary of 16 peer-reviewed journal articles Updated
Hematology · Myelodysplastic Syndromes

The Biology of MDS: Why Your Bone Marrow is Struggling

At a Glance

Myelodysplastic Syndromes (MDS) occur when genetic mutations in bone marrow stem cells cause them to produce defective blood cells. These abnormal cells die before entering the bloodstream, leading to low blood counts. Advanced genetic testing is used to distinguish MDS from reversible mimics.

Understanding the biology of Myelodysplastic Syndromes (MDS) means understanding the difference between a “production” problem and a “quality control” problem. In MDS, your bone marrow is often working overtime to produce blood cells, but the cells it makes are defective and “recalled” before they ever leave the factory [1].

To feel confident in your diagnosis, it helps to understand exactly what is happening in your marrow and how doctors make sure your symptoms aren’t being caused by something else entirely.

The Biological Mechanism: A “Glitch” in the Stem Cells

MDS begins in your hematopoietic stem cells—the “master cells” in your bone marrow that are responsible for creating all your red cells, white cells, and platelets [2].

  1. Somatic Mutations: Over time, these stem cells can develop genetic “typos” called somatic mutations [3]. These mutations act like a corrupted software code, giving the cancer cells a competitive advantage over healthy ones [4].
  2. Ineffective Hematopoiesis: Because of this corrupted code, the cells fail to mature properly. This is known as ineffective hematopoiesis [1].
  3. Inflammatory Cell Death: As these defective cells try to grow, they trigger an inflammatory alarm inside the bone marrow (an inflammasome) [5]. This causes the cells to undergo a form of inflammatory cell death (pyroptosis) before they can enter your bloodstream [6].

The result is a bone marrow that is full of cells (hypercellular), yet your actual blood counts remain low [7].

MDS “Look-Alikes” (Differential Diagnosis)

MDS is often called a “diagnosis of exclusion” because many other conditions can make your blood cells look abnormal (dysplastic) under a microscope. Before confirming MDS, your care team must rule out these “look-alikes”:

  • Nutritional Deficiencies: A lack of Vitamin B12, folate, or copper can perfectly mimic the appearance of MDS [8][9]. For example, taking too much zinc can lead to a copper deficiency, which can cause bone marrow failure that is completely reversible [9].
  • VEXAS Syndrome: This is a recently discovered inflammatory condition caused by a mutation in the UBA1 gene [10]. It often looks like MDS but is distinguished by severe skin rashes, fevers, and “bubbles” (vacuoles) seen inside the bone marrow cells [11][12].
  • Medication and Toxins: Heavy alcohol use or certain medications (like chemotherapy or some antibiotics) can temporarily damage the bone marrow in a way that looks like MDS [9].

How Doctors Confirm it is MDS

Because simply looking at cells isn’t always enough, doctors use three key tools to prove a diagnosis of MDS:

  1. Cytogenetics: This test looks at the physical structure of your chromosomes. Finding a specific structural change (like a missing piece of chromosome 5, known as del(5q)) is a “smoking gun” for MDS [13].
  2. Next-Generation Sequencing (NGS): This advanced test looks for specific gene mutations (like SF3B1, ASXL1, or TP53) [14]. Finding these clonal mutations helps prove the condition is a permanent genetic change rather than a temporary vitamin deficiency.
  3. Flow Cytometry: This tool uses lasers to look at the proteins on the surface of your blood cells [15]. It helps identify the specific “fingerprint” of MDS cells and can distinguish them from other types of bone marrow failure [16].

Common questions in this guide

What causes low blood counts in MDS?
In MDS, bone marrow stem cells develop genetic mutations that act like corrupted software, causing them to produce defective blood cells. These abnormal cells trigger an inflammatory response and die before they can leave the bone marrow, resulting in low blood counts.
Can vitamin deficiencies look like MDS?
Yes, severe deficiencies in Vitamin B12, folate, or copper can perfectly mimic the bone marrow changes seen in MDS. Your doctor will use blood tests to check your vitamin levels and ensure your symptoms are not caused by a reversible nutritional deficiency.
What is VEXAS syndrome and how is it different from MDS?
VEXAS syndrome is an inflammatory condition caused by a UBA1 gene mutation that can mimic MDS in the bone marrow. It is usually distinguished from MDS by the presence of severe skin rashes, fevers, and unique bubbles called vacuoles inside the marrow cells.
How do doctors definitively prove I have MDS?
Because simply looking at cells under a microscope is not always enough, doctors use advanced testing to look for chromosome changes and specific gene mutations. These tests help prove the condition is a permanent genetic change in your stem cells rather than a temporary issue.
Can medications or alcohol cause my bone marrow to look like MDS?
Yes, heavy alcohol use or certain medications, such as some chemotherapy drugs or antibiotics, can temporarily damage the bone marrow. This damage can look very similar to MDS under a microscope, making a thorough medical history essential for an accurate diagnosis.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Have we ruled out common mimics like Vitamin B12, folate, and copper deficiencies with blood tests?
  2. 2.Do I have any specific gene mutations, such as SF3B1 or UBA1, that help confirm this is MDS and not another condition?
  3. 3.Were there any 'vacuoles' seen in my bone marrow cells that might suggest VEXAS syndrome instead of classic MDS?
  4. 4.Does my bone marrow show 'clonal' markers (like chromosome changes), or is the diagnosis based solely on how the cells look under the microscope?
  5. 5.Could any of my current medications or supplements be interfering with my bone marrow's ability to make blood?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (16)
  1. 1

    Introduction to the Review Series on Myelodysplasia.

    Mittelman M

    Haematologica 2025; (110(2)):281-282 doi:10.3324/haematol.2023.284948.

    PMID: 39895333
  2. 2

    Treatments targeting MDS genetics: a fool's errand?

    DeZern AE

    Hematology. American Society of Hematology. Education Program 2018; (2018(1)):277-285 doi:10.1182/asheducation-2018.1.277.

    PMID: 30504322
  3. 3

    Impact of spliceosome mutations on RNA splicing in myelodysplasia: dysregulated genes/pathways and clinical associations.

    Pellagatti A, Armstrong RN, Steeples V, et al.

    Blood 2018; (132(12)):1225-1240 doi:10.1182/blood-2018-04-843771.

    PMID: 29930011
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    Myelodysplasia Syndrome, Clonal Hematopoiesis and Cardiovascular Disease.

    Veiga CB, Lawrence EM, Murphy AJ, et al.

    Cancers 2021; (13(8)) doi:10.3390/cancers13081968.

    PMID: 33921778
  5. 5

    Fueling clonal dominance through TRAFficking of NF-κB signaling.

    Ueda K, Kumari R, Steidl U

    Nature immunology 2020; (21(5)):489-490 doi:10.1038/s41590-020-0662-0.

    PMID: 32313244
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    Myelodysplastic Neoplasms (MDS): Pathogenesis and Therapeutic Prospects.

    Li X, Zou C, Xiang X, et al.

    Biomolecules 2025; (15(6)) doi:10.3390/biom15060761.

    PMID: 40563403
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    Myelodysplastic syndromes: 2021 update on diagnosis, risk stratification and management.

    Garcia-Manero G, Chien KS, Montalban-Bravo G

    American journal of hematology 2020; (95(11)):1399-1420 doi:10.1002/ajh.25950.

    PMID: 32744763
  8. 8

    Hematogones Detected by Flow Cytometry in a Child with Vitamin B12 Deficiency.

    Sutton L, Mba N

    Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 2017; (20(2)):172-175 doi:10.1177/1093526616686241.

    PMID: 28326965
  9. 9

    Dyserythropoiesis in the diagnosis of the myelodysplastic syndromes and other myeloid neoplasms: problem areas.

    Goasguen JE, Bennett JM, Bain BJ, et al.

    British journal of haematology 2018; (182(4)):526-533 doi:10.1111/bjh.15435.

    PMID: 29917221
  10. 10

    VEXAS syndrome in myelodysplastic syndrome with autoimmune disorder.

    Huang H, Zhang W, Cai W, et al.

    Experimental hematology & oncology 2021; (10(1)):23 doi:10.1186/s40164-021-00217-2.

    PMID: 33741056
  11. 11

    Successful azacitidine therapy for myelodysplastic syndrome associated with VEXAS syndrome.

    Kataoka A, Mizumoto C, Kanda J, et al.

    International journal of hematology 2023; (117(6)):919-924 doi:10.1007/s12185-023-03532-y.

    PMID: 36641501
  12. 12

    Molecular and clinical presentation of UBA1-mutated myelodysplastic syndromes.

    Sirenko M, Bernard E, Creignou M, et al.

    Blood 2024; (144(11)):1221-1229 doi:10.1182/blood.2023023723.

    PMID: 38687605
  13. 13

    Computational flow cytometry as a diagnostic tool in suspected-myelodysplastic syndromes.

    Duetz C, Van Gassen S, Westers TM, et al.

    Cytometry. Part A : the journal of the International Society for Analytical Cytology 2021; (99(8)):814-824 doi:10.1002/cyto.a.24360.

    PMID: 33942494
  14. 14

    Risk stratifying MDS in the time of precision medicine.

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    Hematology. American Society of Hematology. Education Program 2022; (2022(1)):375-381 doi:10.1182/hematology.2022000349.

    PMID: 36485160
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    Validation of the diagnostic potential of 17 immunophenotypic core markers defined by the ELN-iMDS-Flow Working Group in an independent cohort of patients with MDS.

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    HemaSphere 2025; (9(3)):e70075 doi:10.1002/hem3.70075.

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    Flow cytometric analysis of erythroid precursors and mutational signatures of lower risk myelodysplastic syndromes identify responders to erythroid stimulating agents.

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    Blood cancer journal 2024; (14(1)):127 doi:10.1038/s41408-024-01112-9.

    PMID: 39112451

This page explains the biology and diagnostic process of Myelodysplastic Syndromes (MDS) for educational purposes. It is not medical advice. Always consult your hematologist or oncologist for an accurate diagnosis and treatment plan.

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