Genetic Predisposition to Myelodysplastic Syndromes: A Challenge for Adult Hematologists

• Published in: International journal of molecular sciences Vol. 22; no. 5; p. 2525
• Main Authors: Crisà, Elena, Boggione, Paola, Nicolosi, Maura, Mahmoud, Abdurraouf Mokhtar, Al Essa, Wael, Awikeh, Bassel, Aspesi, Anna, Andorno, Annalisa, Boldorini, Renzo, Dianzani, Irma, Gaidano, Gianluca, Patriarca, Andrea
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 03-03-2021; MDPI
• Subjects: Adult; Adults; Anemia; Apoptosis; Asymptomatic; Ataxia; Bone marrow; Cancer; Cell cycle; Cell division; Chromosomes; Congenital diseases; Deoxyribonucleic acid; Diagnostic systems; Disease; DNA; DNA damage; DNA repair; Evolution; Genes; genetic predisposition; Genetic Predisposition to Disease - genetics; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic stem cells; Humans; inherited bone marrow failure; Kinases; Male; Mutation; Mutation - genetics; Myelodysplastic syndrome; Myelodysplastic syndromes; Myelodysplastic Syndromes - genetics; Neutropenia; Pathogenesis; Patients; Physiology; Population genetics; Review; Ribosomes; Signal transduction; Stem cell transplantation; Stem cells; Telomerase; Telomeres; Transplantation; Transplants & implants; genetic predisposition; inherited bone marrow failure; myelodysplastic syndromes
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22052525

Myelodysplastic syndromes (MDS) arising in the context of inherited bone marrow failure syndromes (IBMFS) differ in terms of prognosis and treatment strategy compared to MDS occurring in the adult population without an inherited genetic predisposition. The main molecular pathways affected in IBMFS involve telomere maintenance, DNA repair, biogenesis of ribosomes, control of proliferation and others. The increased knowledge on the genes involved in MDS pathogenesis and the wider availability of molecular diagnostic assessment have led to an improvement in the detection of IBMFS genetic predisposition in MDS patients. A punctual recognition of these disorders implies a strict surveillance of the patient in order to detect early signs of progression and promptly offer allogeneic hematopoietic stem cell transplantation, which is the only curative treatment. Moreover, identifying an inherited mutation allows the screening and counseling of family members and directs the choice of donors in case of need for transplantation. Here we provide an overview of the most recent data on MDS with genetic predisposition highlighting the main steps of the diagnostic and therapeutic management. In order to highlight the pitfalls of detecting IBMFS in adults, we report the case of a 27-year-old man affected by MDS with an underlying telomeropathy.