Table 2 The ribosomal defects, cancer susceptibility and treatment in ribosomopathies
From: Ribosomal proteins and human diseases: molecular mechanisms and targeted therapy
Ribosomopathy | Mutated ribosomal genes (% patients with the disease indicated) | Function in ribosome biogenesis | Clinical features | Cancer susceptibility (O/Z ratio) | Treatment |
|---|---|---|---|---|---|
Ribosomopathies associated with ribosomal proteins | |||||
Diamond–Blackfan anemia | RPS19 (25%), large deletion (10-20%), RPL5 (7%), RPS26 (6.6%), RPL11 (5%), RPL35A (3%), RPS10 (3%), RPS24 (2.4%), RPS17 (1%), RPL15, RPS28, RPS29, RPS7, RPS15, RPS27A, RPL9, RPL18, RPL26, RPL27, RPL31, GATA1, HSP70, TSR2 | Pre-rRNA processing, ribosomal subunit synthesis and mRNA translation | Bone marrow failure syndrome characterized by erythroid hypoplasia, congenital anomalies including craniofacial, limb, genitourinary and heart malformations | Overall O/Z ratio: 2.5-5.4. MDS (352), vaginal squamous cell carcinoma (172), Esophageal cancer (65), Colon cancer (45), Osteogenic sarcoma (42), AML (29) | steroids; blood transfusion; HSCT |
Myelodysplastic syndrome (MDS) with chromosome 5q deletion | RPS14 | 18S pre-rRNA processing and 40S ribosomal subunit synthesis | Erythroid hypoplasia, macrocytic anemia, hypolobated megakaryocytes with <5% bone marrow myeloblasts, <1% circulating peripheral blasts and absence of Auer rods | MDS, AML | transfusion; erythropoietin; thalidomide; retinoids; chemotherapy and hypomethylating agents, bone marrow transplantation |
Ribosomopathies associated with other ribosome biogenesis factors | |||||
Shwachman-Diamond syndrome | SBDS (92%), DNAJC21, EFL1 | Release of EIF6 from 60S subunit for 60S maturation | Bone marrow failure featured by neutropenia or multilineage cytopenias, multiple developmental anomalies such as exocrine pancreatic dysfunction and impaired bone development | Overall O/Z ratio 8.5. MDS, AML (202), ovarian cancer (169) | Pancreatic enzyme replacement, GCSF, blood transfusions, HSCT; reconstructive surgery |
X-linked-dyskeratosis congenita | DKC1(25%) | Pre-rRNA psedouridylation | Bone marrow failure usually associated with skin hyperpigmentation, nail dystrophy, mucosal leukoplakia and pulmonary fibrosis | Overall O/Z ratio 4.2. MDS (578), tongue (216), AML (73), and head and neck tumors (74), leukemia (24) | Androgen, blood transfusion; HSCT; |
Cartilage hair hypoplasia–anauxetic dysplasia | RMRP | Pre-rRNA processing | Short stature, bone marrow failure, hair hypoplasia and defective immunity | Overall O/Z ratio 7. Non-Hodgkin lymphoma (100) and basal cell carcinoma (33) | Blood transfusion; reconstructive surgery, HSCT |
Treacher Collins Syndrome | TCOF1, POLR1C and POLR1D | Pre-rRNA transcription and modification | Craniofacial malformations | NA | reconstructive surgery |
