Abstract
Pediatric myelodysplastic syndrome (MDS) is an uncommon disease and little is known about the molecular alterations of its development and evolution to acute myeloid leukemia (AML). The Enhancer of Zeste Homolog 2 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 (PCR2). It is a histone methyltransferase, that targets lysine 27 of histone 3. This methylated H3–K27 is usually associated with the silencing of genes that are involved in fundamental cellular processes, such as cell proliferation and differentiation. There are only few studies showing the status of EZH2 expression in patients with MDS and they were performed in adult MDS patients. The aim of this study was to analyze the EZH2 expression in pediatric patients with MDS and its association with karyotypes and evolution to acute myeloid leukemia (AML). We conducted the first study of EZH2 expression in pediatric patients with MDS. Considering the EZH2 expression levels in 42 patients and 17 healthy pediatric donors, it was possible to define three groups of expression in patients: low, intermediate, and high. The intermediate level encompassed patients with normal karyotypes, low level included patients with monosomy 7 and del(7q) and high level included patients with trisomy 8 and del(11q) (p < 0.0001). Comparing the leukemic evolution, the low expression group presented disease evolution in 100% (8/8) of the cases, the intermediate expression group showed disease evolution in 4.34% (1/23) and in the high expression group, 63.63% (7/11) patients showed evolution from MDS to AML (p < 0.0001). It is important to note that low and high EZH2 expression are associated with leukemic evolution, however low expression showed a stronger association with evolution from MDS to AML than the high expression. Our results suggest a scale of measure for EZH2 expression in pediatric MDS, where aberrant EZH2 expression may be a potential biomarker of disease evolution.
Highlights
Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematological neoplasms with a variable clinical features and diverse genetic and epigenetic alterations. e major clinical MDS characteristics are ine ective hematopoiesis, dysplasias, peripheral cytopenias, and an increased risk of transformation to acute myeloid leukemia (AML) [1]
It is important to observe that we found other karyotypes, as we can see in Figure 1, but we considered normal karyotypes, monosomy 7/del(7q) and trisomy 8/del(11q) for the association analysis with Enhancer of Zeste Homolog 2 (EZH2) expression, because of the number of patients in these cytogenetic groups (Table 2)
It is interesting to note that cytogenetic analysis showed, as main numerical chromosomal abnormality, the trisomy 8 and it was not detected the alterations in chromosome 7. e authors suggested that increased expression of Polycomb genes, including the EZH2, is an event related to poor prognosis in MDS [13]
Summary
Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematological neoplasms with a variable clinical features and diverse genetic and epigenetic alterations. e major clinical MDS characteristics are ine ective hematopoiesis, dysplasias, peripheral cytopenias, and an increased risk of transformation to acute myeloid leukemia (AML) [1]. Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematological neoplasms with a variable clinical features and diverse genetic and epigenetic alterations. In pediatric patients with MDS, the clonal cytogenetic alterations can be detected in 50–70% of the cases [5]. E cytogenetic evaluation of a bone marrow sample from patients with MDS has become an integral part of BioMed Research International clinical care [5,6,7]. There is a percentage of patients with normal karyotypes. It is important a molecular characterization of genetic and epigenetic alterations associated with the evolution of the disease, which could help predict prognosis
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