Shwachman-Diamond Syndrome: Molecular Mechanisms and Current Perspectives
AbstractShwachman-Diamond syndrome (SDS) is a rare inherited disease mainly caused by mutations in the Shwachman-Bodian-Diamond Syndrome (SBDS) gene. However, it has recently been reported that other genes, including DnaJ heat shock protein family (Hsp40) member C21 (DNAJC21), elongation factor-like 1 (EFL1) and signal recognition particle 54 (SRP54) are also associated with an SDS-like phenotype. Interestingly,SBDS, DNAJC21, EFL1 andSRP54 are involved in ribosome biogenesis: SBDS, through direct interaction with EFL1, promotes the release of the eukaryotic initiation factor 6 (eIF6) during ribosome maturation,DNAJC21 stabilizes the 80S ribosome, andSRP54 facilitates protein trafficking. These findings strengthen the postulate that SDS is a ribosomopathy. SDS is a multiple-organ disease mainly characterized by bone marrow failure, bone malformations, pancreatic insufficiency and cognitive disorders. Almost 15 –20% of patients with SDS present myelodysplastic syndrome with a high risk of acute myeloid leukemia (AML) transformation. Unfortunately, besides bone marrow transplantation, no gene-based therapy for SDS has yet been developed. This review aims to recapitulate the recent findings on the molecula r mechanisms of SDS underlying bone marrow failure, hematopoiesis and AML development and to draw a realistic picture of current perspectives.
Source: Molecular Diagnosis and Therapy - Category: Molecular Biology Source Type: research
More News: Acute Leukemia | Acute Myeloid Leukemia | Bone Marrow Transplant | Genetics | Leukemia | Molecular Biology | Myelodysplastic Syndrome | Pancreas | Transplants