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myelodysplastic/myeloproliferative neoplasms

Monday 8 December 2003


Definition: The myelodysplastic syndromes are all disorders of the stem cell in the bone marrow.


- Auer rod in RAEB2 myelodysplasia



The system used today is the World Health Organization (WHO) classification. This system seems to be more helpful than the FAB classification in predicting prognosis (outlook). The WHO system recognizes 7 types of MDS:

- refractory cytopenia with unilineage dysplasia (RCUD)
- refractory anemia with ringed sideroblasts (RARS)
- refractory cytopenia with multilineage dysplasia (RCMD)
- refractory anemia with excess blasts-1 (RAEB-1)
- refractory anemia with excess blasts-2 (RAEB-2)
- myelodysplastic syndrome, unclassified (MDS-U)
- myelodysplastic syndrome associated with isolated del(5q)

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)

The myelodysplastic syndromes (MDS, formerly known as preleukemia) are a diverse collection of hematological (blood-related) medical conditions that involve ineffective production (or dysplasia) of the myeloid class of blood cells (myelodysplasia).

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.

Clinical synopsis

Patients with MDS often develop severe anemia and require frequent blood transfusions. In most cases, the disease worsens and the patient develops cytopenias (low blood counts) caused by progressive bone marrow failure.

The outlook in MDS is poor, and most patients will progress within a few months to refractory acute myeloid leukemia. The median survival varies from years to months.


The myelodysplastic syndromes are all disorders of the stem cell in the bone marrow. In MDS, hematopoiesis (blood production) is disorderly and ineffective. The number and quality of blood-forming cells decline irreversibly, further impairing blood production.

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.

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 (The International Prognostic Scoring System - RCMD). The WHO classification for MDS is now widely accepted.

Old system New system
Refractory anemia (RA) Refractory cytopenia with unilineage dysplasia (Refractory anemia, Refractory neutropenia, and Refractory thrombocytopenia)
Refractory anemia with ringed sideroblasts (RARS) Refractory anemia with ring sideroblasts (RARS) / Refractory anemia with ring sideroblasts - thrombocytosis (RARS-t) (provisional entity) which is in essence a myelodysplastic/myeloproliferative disorder and usually has a JAK2 mutation (janus kinase) - New WHO classification 2008
- Refractory cytopenia with multilineage dysplasia (RCMD) includes the subset Refractory cytopenia with multilineage dysplasia and ring sideroblasts (RCMD-RS). RCMD includes patients with pathological changes not restricted to red cells (i.e., prominent white cell precursor and platelet precursor (megakaryocyte) dysplasia.
Refractory anemia with excess blasts (RAEB) Refractory anemia with excess blasts I and II. RAEB was divided into *RAEB-I (5-9% blasts) and RAEB-II (10-19%) blasts, which has a poorer prognosis than RAEB-I. Auer rods may be seen in RAEB-II which may be difficult to distinguish from acute myeloid leukemia.
Refractory anemia with excess blasts in transformation (RAEB-T) The category of RAEB-T was eliminated; such patients are now considered to have acute leukemia. 5q- syndrome, typically seen in older women with normal or high platelet counts and isolated deletions of the long arm of chromosome 5 in bone marrow cells, was added to the classification.
Chronic myelomonocytic leukemia (CMML) CMML was removed from the myelodysplastic syndromes and put in a new category of myelodysplastic-myeloproliferative overlap syndromes.
- 5q- syndrome
- Myelodysplasia unclassifiable (seen in those cases of megakaryocyte dysplasia with fibrosis and others)
- Refractory cytopenia of childhood (dysplasia in childhood) - New WHO classification 2008

Myelodysplastic syndrome unclassified

WHO proposed criteria for diagnosis and classification of MDS apply to most cases. However, occasional cases are difficult to classify into defined categories because of one or more unusual features:
- I- Rare cases with less than 5% blast will present with auer rods. These cases usually have the features of RAMD.
- II- Occasionally cases of MDS present with isolated neutropenia or thrombocytopenia without anemia and with dysplastic changes confined to the single lineage. The term "refractory neutropenia" and "refractory thrombocytopenia" have sometimes used to describe these cases. A diagnosis of MDS in patients with neutropenia or thromobocytopenia without anemia should be made with caution.
- III- Patients with RA or RAEB occasionally present with leukocytosis or thrombocytosis instead of usual cytopenia.


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.


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.


- therapy-related myelodysplasia


- cytogenetical anomalies in 50% of cases of myelodysplastic syndrome (MDS) and 80% of cases of secondary MDS (following chemotherapy or radiotherapy)
- partial or complete chromosome deletion or addition

  • del5q
  • -7
  • +8
  • -Y
  • del20q

- balanced translocations

  • MDS1-EVI1 in t(3;3) or t(3;21) translocations
  • TEL in t(5;12)
  • HIP1 in t(5;7)
  • MLF1 in t(3;5)
  • MEL1 in t(1;3)


- Fenaux P. Chromosome and molecular abnormalities in myelodysplastic syndromes. Int J Hematol. 2001 Jun;73(4):429-37. PMID: 11503956

See also

- stem-cell diseases


- Genetics of myelodysplastic syndromes: new insights. Graubert T, Walter MJ. Hematology Am Soc Hematol Educ Program. 2011;2011:543-9. PMID: 22160087 (Free)

- 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