Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There are several common themes that are emerging from our expanding knowledge about the inherited bone marrow failure syndromes. Patients have a spectrum of birth defects, which are relatively characteristic for each syndrome. but overlap in features such as poor growth. radial ray anomalies, and involvement of skin, eyes, renal, cardiac, skeletal, and other organs. Within each syndrome the composition and severity of the physical phenotype varies widely, and it may require the astute observer to make the correct diagnoses in the milder cases. There is also a wide spectrum to the hematologic picture. These range from single cytopenias such as DBA, SCN, and TAR, which do not develop pancytopenia, to SD and Amega patients who begin with deficiency of a specific single lineage, but evolve to aplastic anemia, to patients with FA or DC, who may present with a deficiency of any one of the cell lines, but almost inevitably end up with full-blown aplastic anemia. Acute myeloid leukemia has been observed in FA, DBA, DC, SD, SCN, and Amega, although not yet in TAR patients. MDS has also been reported in all of the same disorders as AML, although whether it is a preleukemic condition or an independent bone marrow dyspoiesis is not yet clear. Solid tumors are also now appearing in patients whose underlying disease involves hematopoiesis and physical development. These tumors occur at much younger ages than in the general population, in patients who do not appear to have the usual risk factors, and have patterns that are characteristic to the syndrome, such as head and neck and gynecologic cancers in FA and DC, and osteogenic sarcomas in DBA. The other syndromes have not yet been reported to have a propensity for solid tumors. Several genes have been identified that are mutant in some of the syndromes, although the pathophysiology is still not entirely clear. The inheritance patterns include X-linked recessive, autosomal dominant, autosomal recessive, and even mitochondrial. The FA gene products appear to cooperate, and are important in the pathways involved in response to DNA damage. However, the role of this pathway in developmental defects, hematopoietic failure, and the specific malignancies in FA is not fully elucidated. The DC gene products are important for maintenance of telomere length, which may have relevance to development of aplastic anemia and malignancies, but the relation to the physical phenotype is less apparent. The role of mutations in c-mpl in Amega is more straightforward. since the gene codes for the receptor for thrombopoietin. which is the hormone required for megakaryocyte and platelet development; patients with mutant c-mpl do not have birth defects. The role of mutations in RPS19 in erythropoiesis or developmental defects in DBA patients is not obvious, and the increased frequency of osteogenic sarcomas suggests that at least that subset of patients may have a mutant tumor suppressor gene (such as p53, the mutant gene in Li-Fraumeni syndrome) [68]. Although patients with SCN have mutations in neutrophil elastase, patients with similar mutations may have relatively benign cyclic neutropenia, or may even have normal neutrophil levels [69,70]. The mitochondrial gene deletions in Pearson's Syndrome result in variable degrees of acidosis, and varied organ involvement due to heteroplasmy. Thus, the disorders included under the rubric "inherited bone marrow failure syndromes" have clinical. hematologic, oncologic, and genetic diversity.
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PMID:Bone marrow failure syndromes in children. 1243 Jun 21

The Pur protein family consists of four known members in humans, the prototype gene for which is strongly conserved throughout evolution. Several investigations have now implicated Pur alpha in pathways of inhibition of oncogenic transformation. Clues to the potential importance of Pur family members in cancer are derived from observations of genetic alterations of both Pur alpha and Pur beta in myelodysplastic syndrome progressing to acute myelogenous leukemia. A role for newly-discovered Pur gamma in neoplasia is also beginning to emerge as studies have indicated that cellular levels of two Pur gamma isoforms are elevated in certain tumors. A variety of studies have now implicated Pur alpha in development of blood cells and cells of the central nervous system. Clues to the functions of Pur alpha, a key family member, have recently been derived from studies of the interactions of HIV-1 and JC virus (JCV) in AIDS. JCV causes an opportunistic infection in the brains of certain HIV-1-infected individuals. Pur alpha can influence this viral interaction through functional associations with the Tat protein and TAR RNA of HIV-1, and with large T-antigen and DNA regulatory regions of JCV. Evidence is now strong that Pur alpha interacts with both DNA and RNA and that an important aspect of its function is to recruit regulatory proteins to specific nucleic acid sequences in processes as diverse as DNA replication, gene transcription, RNA transport in the cytoplasm and compartmentalized mRNA translation.
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PMID:The Pur protein family: clues to function from recent studies on cancer and AIDS. 1289 83