MDS is any one of a heterogeneous group of hematopoietic stem cell disorders characterized by cytologic dysplasia in the bone marrow and blood and by various combinations of anemia, neutropenia, and thrombocytopenia. (Medscape)

These disorders have in common the progressive evolution of a monoclonal population of hematopoietic cells, usually involving multiple lineages, generally with accompanying suppression of normal hematopoiesis.

The natural history of these syndromes varies widely, ranging from chronic anemias with a low propensity for leukemic conversion to syndromes with severe hematologic disturbances and a high risk of progression to AML.

The examination of well-prepared peripheral blood smears, bone marrow aspirate smears, and bone marrow biopsy specimens can usually confirm the diagnosis of MDS. The marrow should be at least normocellular for the patient?s age, and cytologic evaluation of the blood and aspirate smear should show dysplasia in at least one cell line. It should be emphasized that these abnormalities are not specific to MDS but can be seen in a variety of other inherited and acquired hematologic disorders. Care must be taken to exclude these other processes before making a diagnosis of MDS. There is overlap between hypocellular MDS and autoimmune aplastic anemia.

A variety of terms, including preleukemia, smoldering or subacute leukemia, dysmyelopoietic syndrome, and myelodysplasia, have all been used to describe MDS.

There is considerable evidence that these disorders are clonal and neoplastic from their earliest detection. Thus, the term preleukemia seems inappropriate, because it implies a premalignant condition. Rather, these disorders are better considered to be a chronic or smoldering leukemia.

There is considerable overlap with other morphologically determined diseases, particularly those categorized as chronic myeloproliferative disorders (CMPDs).

Whereas differentiation of hematopoiesis is qualitatively unimpaired in CMPDs, at least in their early stages, MDS is characterized chiefly by impaired differentiation. Thus, one can speculate that MDS results from alterations of genes that control transcription and cellular differentiation and survival rather than those that regulate cell proliferation.

FAB and WHO classifications

In 1982, the FAB group attempted to standardize the classification of MDS patients by use of criteria based on cytology and the number of blast cells in the marrow and peripheral blood.

In 1996, another important subset was described: refractory cytopenia with multilineage dysplasia (RCMD).

The WHO classification for MDS is now widely accepted.

Progression

In some patients, there is a natural progression of disease between categories as cellular maturation becomes more arrested and blast cells accumulate. In other patients, however, the diagnostic category does not change during the patient?s lifespan.

Increased use of cytogenetic analysis and the development of new techniques for assessing clonality are proving useful not only for diagnosis but also for providing insights into pathogenesis and patterns of responsiveness to growth factors and possible differentiation-inducing agents.

Considerable data suggest that MDS results from combined defects of both stroma and hematopoietic stem cells.

SUbtypes

Several clinical syndromes that may have a more predictable natural history can now be defined.

For example, a deletion of the long arm of chromosome 5 can be detected in some older patients, especially women, with a macrocytic refractory anemia (RA). The platelet count is typically normal or elevated. The bone marrow picture in the RA with 5q minus syndrome is characterized by the presence of monolobulated and bilobulated micromegakaryocytes. Two thirds of these patients have RA or RA with ringed sideroblasts (RARS), and the remainder have RA with excess of blasts (RAEB). In those patients who have a del(5q) as their sole cytogenetic abnormality, MDS tends to follow a more benign course, although progression to AML may occur.

Although MDS is not commonly seen in patients younger than 50 years, there are two distinct pediatric syndromes of importance: juvenile chronic myelomonocytic leukemia (JMML) and the monosomy 7 syndrome.

See also

 stem-cell diseases

References

 Corey SJ, Minden MD, Barber DL, Kantarjian H, Wang JC, Schimmer AD. Myelodysplastic syndromes: the complexity of stem-cell diseases. Nat Rev Cancer. 2007 Feb;7(2):118-29. PMID: 17251918