Myelodysplastic syndromes

Etiology and pathogenesis

Myelodysplastic syndromes may develop as an independent pathology — in this case, they are referred to as primary forms of the disease. However, they frequently arise secondary to prior exposures, forming secondary MDS. The main factors provoking secondary forms include prolonged use of certain medications, exposure to ionizing radiation, and contact with various toxic agents.

The key link in the pathogenesis is a mutation at the level of the pluripotent hematopoietic stem cell. These clonal abnormalities trigger a cascade of changes leading to ineffective hematopoiesis. The paradox of the disease is that the bone marrow remains normocellular or even becomes hypercellular — meaning the cells actively divide. However, due to dysplasia, they are incapable of normal maturation and full functioning. As a result, an insufficient number of mature blood cells enters the peripheral blood, which clinically manifests as pronounced cytopenia: the patient is diagnosed with anemia, leukopenia, and/or thrombocytopenia.

Morphological manifestations of dysplasia

The morphological picture of myelodysplastic syndromes is based on identifying signs of dysplasia in the main hematopoietic lineages.

1. Dyserythropoiesis affects the erythroid lineage. Bone marrow aspirates reveal multinucleated erythroblasts, ring sideroblasts, and cells with signs of nuclear disintegration (karyorrhexis). Asynchronous maturation of the nucleus and cytoplasm is characteristic, and cytoplasmic vacuolization is frequently observed. In the peripheral blood, these abnormalities manifest as changes in erythrocyte size (anisocytosis) and alterations in their normal shape (poikilocytosis).
2. Dysgranulopoiesis reflects pathology of the granulocytic series. The main changes concern neutrophils: their nuclei may acquire an unusual ring-like shape or become hypersegmented. A sharp decrease in the number of specific granules, up to their complete absence, is noted in the cytoplasm of such cells.
3. Dysmegakaryocytopoiesis characterizes abnormalities in the megakaryocytic lineage. Atypical forms appear in the bone marrow: abnormally small micromegakaryocytes, cells containing only a single nucleus, as well as megakaryocytes with multiple small scattered nuclei.

Classification and mixed forms

According to the World Health Organization (WHO) classification from 2000, myelodysplastic syndromes are subdivided into several nosological forms depending on the predominant morphological changes and the number of blast cells:

• Refractory anemia. It has two variants of the clinical course: with the presence of ring sideroblasts in the bone marrow and without them.
• Refractory cytopenia (MDS) presenting with multilineage dysplasia, i.e., involving several hematopoietic lineages simultaneously.
• Refractory anemia (MDS) with excess blasts.
• 5q-syndrome — a specific variant associated with a particular chromosomal abnormality.
• Unclassifiable myelodysplastic syndrome.

It is worth separately mentioning mixed disorders. Their essence lies in the simultaneous combination of myelodysplastic and myeloproliferative features. Such conditions are characterized by abnormalities of granulocytic and monocytic lineage cells, and the disease itself features a moderately aggressive clinical course.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Mechanisms of development of ineffective hematopoiesis at the cellular level
• Differences between primary and secondary myelodysplastic syndromes
• Diagnostic criteria for 5q-syndrome
• Mixed myelodysplastic and myeloproliferative disorders
• Pathogenesis of ring sideroblast formation

Other topics in Hematopoietic System Diseases

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