Chronic myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) are a group of diseases of the bone marrow (BM), the organ responsible for producing blood cells (red blood cells, white blood cells, platelets). Under normal circumstances these cells reproduce and mature in the bone marrow before then circulating in the blood. With MDS/MPN the bone marrow produces these cells abnormally, in terms of number, maturation and function, and these anomalies can be detected when the blood is analysed under the microscope.

In the case of MDS there is usually a decrease in the number of some blood cells with some morphological alterations (dysplasia) and in the case of MPN there is usually an increase (proliferation) of blood cells. MDS/MPN are a combination of these two kinds of alteration in varying degrees and some degree of dysplasia in the blood cells and in the bone marrow is always found. Proliferation manifests itself through an increase in the number of leukocytes (leukocytosis), platelets (thrombocytosis) and/or red blood cells (polycythemia); dysplastic alterations may be accompanied by macrocytic anemia (very large red blood cells), and a decrease in the number of white blood cells (leukopenia) and/or in the number of platelets (thrombocytopenia).

Similarly, the sick cells affected by MDS/MPN combine alterations of mechanisms implicated in both MDS and MPN; in the case of MDS there are DNA alterations that affect chromosomes, genes (mutations) and methylation (modifications of the DNA that may deactivate a gene's function) as well as other structures relating to DNA; in the case of MPN there are usually genetic alterations (mutations) such that the sick cell's "programme" (metabolism) functions at a faster rate than normal, being responsible for some of the patient's symptoms.

The causes of MDS/MPN are unknown, but in most cases they are diseases associated with aging, environmental exposure to toxic substances (through work or otherwise), or treatments such as radiotherapy and/or chemotherapy, amongst others.

The World Health Organisation (WHO) classifies the following subtypes of MDS/MPN:

1) Chronic myelomonocytic leukemia (CMML), the most frequent form in which an increase in the number of monocytes, a subtype of leucocyte, predominates;

2) Atypical chronic myeloid leukaemia (aCML), BCR/ABL1 negative (very rare);

3) Juvenile myelomonocytic leukaemia (during childhood);

4) Myelodysplastic/myeloproliferative neoplasm with ringed sideroblasts (abnormal distribution of iron in the red blood cell) and thrombocytosis;

5) Unclassifiable MDS/MPN (when the alterations observed in the blood and the bone marrow do not enable diagnosis as either an MDS or an MPN, nor one of the MDS/MPN as defined by the WHO).

If there is anemia on account of a decrease in the number of red blood cells, frequent symptoms include tiredness and weakness (when this is more significant there can also be dizziness, palpitations, perspiration, amongst others). In more serious cases there may be symptoms deriving from a decrease in the number of white blood cells and/or platelets leading to infections and/or hemorrhages respectively. When proliferative alterations predominate there is a risk of thrombosis because the increase in the number of red blood cells and/or platelets may lead to the blockage of the blood vessels, especially if the person smokes, has a high cholesterol level, or high blood pressure. Furthermore, given that the bone marrow works at a higher rate than normal, the liver and spleen may increase in size and contribute to this proliferation. Such an increase in size may cause discomforts such as swollen stomach, stomach ache, constipation, etc. There may also be symptoms, known as constitutional symptoms, such as fatigue, loss of appetite, weight loss and itchiness.

The following tests are required in order to diagnose MDS/MPN:

1) analysis of blood cells under the microscope in order to see the alterations and determine the number and shape of the cells;

2) bone marrow aspiration to determine whether the blood cell precursors are present in much larger numbers than normal and whether there are alterations in their shape or size; to see whether there is a variable percentage of abnormal immature cells (blasts) with possible chromosomal and genetic alterations and, lastly, to see whether there are ringed sideroblasts or not, and

3) a bone marrow biopsy to confirm the diagnosis, and to see whether there has been a considerable increase in the number of cells in the bone marrow, and to establish whether there is a light to moderate degree of fibrosis (a kind of 'net' or 'membrane' that impedes its normal functioning). The fact that the same patient may present both dysplastic and proliferative alterations can hinder the classification of the disease as defined by the categories established for MDS/MPN by the WHO, as well as making it difficult to distinguish clearly between MDS and MPN.

For more quality information about myelodysplastic syndromes, you can consult the following websites:

• Myelodysplastic syndromes treatment. National Cancer Institute

• What are Myelodysplastic syndromes? National Cancer Institute.

There are other resources and links of interest that may be of use to myelodysplastic syndrome patients:

There are other resources and links of interest that may be of use to adult acute myeloid leukaemia patients:

• Bone marrow transplant guide. Fundación Josep Carreras

• Graft-versus-host disease. Leukaemia and Lymphoma Society

• Fertility and treatment information. Leukaemia and Lymphoma Society