**3. Myelodysplastic syndrome**

The primary myelodysplastic syndrome (MDS) comprises a heterogeneous group of clonal bone marrow disorders, characterized by abnormal cellular morphology (dysplasias) and defects in the normal differentiation and prolileration of hematopoietic precursors. These

5-azacytidine and 5-aza-2'-deoxycytidine, have been indicated as a promising new treatment for cancer (Streseman & Lyko, 2008). Histone deacetylase inihibitors (HDACs) have also been analyzed at clinical protocols for solid tumors (breast, non-small lung cells, prostatic cancer) and mainly for hematological malignancies (myelomas, leukemias and myelodysplastic syndrome) (Ellis et al., 2009; Graham et al., 2009; Hrebackova et al., 2010; Razak et al., 2011). In figure 3, we can see that the epigenetic therapy can "re-programmed"

Fig. 3. Epigenetic therapy acting in the effects of DNMT or HDAC. Inhibitors of DNMT (*DNA methyltransferase*) or HDAC (*histone deacetylases*), as DMI (*DNMT inhibitor*) and HDI (*Histone Deacetylase Inhibitor*), respectively, induce the reprogramming expression by chromatin decompression. In summary, these inhibitors act mainly cell-cycle, apoptosis and

The primary myelodysplastic syndrome (MDS) comprises a heterogeneous group of clonal bone marrow disorders, characterized by abnormal cellular morphology (dysplasias) and defects in the normal differentiation and prolileration of hematopoietic precursors. These

gene expression patterns.

differentiation related genes.

**3. Myelodysplastic syndrome** 

defects result in ineffective hematopoiesis (bone marrow failure) and an increased risk of transformation into acute myeloid leukemia (AML) (Davids & Steensma, 2010; Jadersten & Hellström-Lindberg, 2008). MDS is viewed as a disease of adults, particularly the elderly. Pediatric MDS is an uncommon disorder, accounting for less than 5% of hematopoietic malignancies (Elghetany, 2007; Niemeyer & Baumann, 2008). The primary MDS presents a natural history since an indolent disease with long time of duration to a rapid progression to AML in few months (Nishino & Chang, 2005). The diagnosis is done initially by the hemogram indicating one or more cytopenias in peripheral blood like anemia, neutropenia and thrombocytopenia. The analysis is performed by the myelogram and bone marrow biopsy to identify dysplastic cells, the possible presence of blasts, characterizing later stages of the disease, and the presence of abnormal localization of immature precursors (ALIP). The bone marrow of MDS patients is usually hypercellular or normocellular, but there are a small number of cases with hypocellular bone marrow. In cases where bone marrow is hypocellular, it is recommended to perform differential diagnosis of severe aplastic anemia (SAA) and paroxysmal nocturnal hemoglobinuria (PNH). In these cases, important diagnostic tools, like the cytogenetics and the immunophenotyping, aid this diagnosis (Bennett & Orazi, 2009; Wong & So, 2002). The apparent paradox of hypercellular bone marrow and peripheral blood cytopenias was clarified by studies showing that MDS patients have increased rates of apoptosis in bone marrow in early stages of the disease (Parker et al., 2000).

The primary MDS diagnosis is considered a difficult clinical practice, because there are several clinical manifestations which may present a clinical and histological picture quite similar to MDS, such as nutritional deficiencies, infections and congenital conditions. It is necessary a differential diagnosis, where the presence of cytogenetic clonality helps in the diagnosis of primary MDS and contributes for the prognosis (Haase et al., 2007; Olney & Le Beau, 2009; Solé et al., 2005; Tiu et al., 2011). Nevertheless, there are cases with normal karyotype, so it is important to characterize molecular biomarkers to aid the MDS diagnosis. Because the primary MDS is a disease extremely heterogeneous, the definition of prognostic factors are often difficult. Thus, in the later years, it has been extensively discussed the classifications and prognostic scales for adult and pediatric patients.
