Germline and somatic genetic landscape of pediatric myelodysplastic syndromes

Pediatric myelodysplastic syndromes myelodysplastic syndromes: (my-eh-lo-diss-PLASS-tik SIN-dromez) A group of disorders where the bone marrow does not work well, and the bone marrow cells fail to make enough healthy blood cells. Myelo refers to the bone marrow. Dysplastic means abnormal growth or development. People with MDS have low blood cell count for at… (MDS) represent a rare group of clonal hematopoietic stem cell disorders accounting for ~5% of pediatric hematological malignancies. They are characterized by ineffective hematopoiesis hematopoiesis: (hi-mat-uh-poy-EE-suss) The process of making blood cells in the bone marrow. , cytopenia cytopenia: (sie-tuh-PEE-nee-uh) A shortage of one or more blood cell types. Also called a low blood count. , and dysplastic changes in the bone marrow bone marrow: The soft, spongy tissue inside most bones. Blood cells are formed in the bone marrow. with variable risk of progression to acute myeloid leukemia acute myeloid leukemia: (uh-KYOOT my-uh-LOYD loo-KEE-mee-uh) A cancer of the blood cells. It happens when very young white blood cells (blasts) in the bone marrow fail to mature. The blast cells stay in the bone marrow and become to numerous. This slows production of red blood cells and platelets. Some cases of MDS become… . Unlike adult MDS, pediatric cases predominantly present with hypocellular hypocellular: A condition in which there are too few cells, for example, within the bone marrow. Patients with aplastic anemia have hypocellular bone marrow. bone marrow, with monosomy 7 monosomy 7: Describes the loss of one of the two number 7 chromosomes. "Mono" means one and "somy" comes from the word chromosome. A laboratory test called fluorescence in situ hybridization (FISH) detects monosomy 7 and other genetic abnormalities. Monosomy 7 can occur in adult patients… and trisomy 8 as the most common cytogenetic aberrations. Pediatric MDS can manifest as primary disease or arise secondary to classical inherited bone marrow failure bone marrow failure: A condition that occurs when the bone marrow stops making enough healthy blood cells. The most common of these rare diseases are aplastic anemia, myelodysplastic syndromes (MDS) and paroxysmal nocturnal hemoglobinuria (PNH). Bone marrow failure can be acquired (begin any time in life) or can be… syndromes, prior cytotoxic therapy, or acquired aplastic anemia aplastic anemia: (ay-PLASS-tik uh-NEE_mee-uh) A rare and serious condition in which the bone marrow fails to make enough blood cells - red blood cells, white blood cells, and platelets. The term aplastic is a Greek word meaning not to form. Anemia is a condition that happens when red blood cell count is low. Most… . In recent years, new germline syndromes have been identified in a substantial proportion of patients with "primary" MDS. The most common are GATA2 deficiency and SAMD9/SAMD9L syndromes, accounting for at least 7% and 8%, respectively. The somatic mutational landscape is different from adult MDS, with recurrent mutations affecting SETBP1, ASXL1, RUNX1, and RAS pathway genes (PTPN11, NRAS, KRAS, CBL), while mutations in spliceosome components and epigenetic regulators which are common in adults, are virtually absent in children. Monosomy 7 serves as a "central hub" in disease evolution, associating with somatic leukemia driver mutations. On the other hand, somatic UBTF-TD and NPM1 mutations define a subtype of MDS with excess blasts blasts: See Blast Cells. with predominantly normal karyotype without known germline predisposition. Hematopoietic stem cell transplantation is the only curative option for pediatric MDS. Understanding the unique genetic profile of pediatric MDS has implications for diagnosis, therapy, donor selection and longterm surveillance, particularly for patients with germline predisposition syndromes. This review discusses current classification systems (WHO and ICC), provides a detailed overview of the germline and somatic genetic landscape of pediatric MDS, and highlights clinical implications of these genetic alterations.