Supervisors info:
Ευγένιος Γουσέτης, Εξωτερικός Συνεργάτης, Ιατρική Σχολή, ΕΚΠΑ
Τζέτη Μαρία, Καθηγήτρια γενετικής, Ιατρική Σχολή, ΕΚΠΑ
Μητράκος Αναστάσιος, Διδάκτωρ, Ιατρική Σχολή, ΕΚΠΑ
Summary:
BACKGROUND: Myelodysplastic syndromes (MDS) are a heterogenous group of clonal disorders characterized by ineffective and dysplastic hematopoiesis and the risk of leukemic transformation. According to the latest WHO classification, there are three main recognised subtypes of MDS, Refractory Cytopenia of Childhood (RCC <5% blasts in bone marrow), Refractory Anemia with Excess Blasts (RAEB 5-19% blasts) and Refractory Anemia with Excess blasts in Transformation (RAEB-T 20-29% blasts in bone marrow). The most common subtype is RCC. In terms of pathogenesis, MDS are distinguished in primary or de novo MDS and in secondary MDS. Secondary MDS occur following chemotherapy and/or radiation therapy or develop on the grounds of inherited bone marrow failure syndromes (IBMFs). Another special group comprises familial MDS. The underlying genetic background of MDS has not yet been elucidated.
ΑΙΜ: The aim of this master thesis is the investigation of the etiology and in particular, the molecular pathophysiology of myelodysplastic syndromes in pediatric patients, focusing on the identification of somatic and germline mutations of the genes involved in the emergence of these syndromes
METHODOLOGY: For the purposes of this thesis, bibliographical research was carried out in online available data bases with the use of keywords
RESULTS: Monosomy 7 occurs in approximately 30% of primary MDS in childhood and in approximately 50% of therapy related MDS (t-MDS). SAMD9/SAMD9L mutations and GATA2 haploinsufficiency are implicated for 8% and 7% of MDS in children respectively. The incidence of germline mutations of RUNX1, CEBPA, DDX41, ETV6, ANKRD26 genes, inherited bone marrow failure syndromes, RAS gene mutations, is also important, leading to emergence of myelodysplasia and increased progression to myeloid malignancy.
CONCLUSIONS: Myelodysplastic syndromes are a rare entity in childhood. Genetic testing is an essential tool for the diagnostic evaluation of de novo or inherited mutations of these syndromes. In addition, this radically contributes to effective treatment plan formation, selection of the appropriate marrow transplant donor, as well as the evaluation of the risk family members are subject to. The molecular imprinting of the mechanisms that lead to the appearance of these syndromes is constantly being enriched, perhaps leading in the future to more favourable conditions for more targeted treatments and optimization of patient care.
Keywords:
Myelodysplastic syndromes, Pediatric myelodysplastic syndromes, Molecular pathophysiology, Genetic predisposition of myelodysplastic syndromes, Refractory cytopenia of childhood
