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)

The Interferon Regulatory Factor (IRF) family consists of multiple transcription factors involved in the regulation of a variety of biological processes. Originally identified as transcriptional regulators of the type I interferon system, IRFs play a pivotal role in adaptive immunity, cell growth, differentiation and tumorigenesis. Hence, understanding IRF biology has important implications in the host response to cancer development and progression. Many lines of evidence suggest that different IRFs are involved in the pathogenesis of Chronic Myeloid Leukemia (CML), a myeloproliferative disorder caused by the BCR-ABL oncoprotein. BCR-ABL displays constitutive tyrosine kinase activity that favors cell proliferation, inhibits apoptosis and allows cell survival even in the absence of proper adhesion to the extracellular matrix. Different BCR-ABL tyrosine kinase inhibitors are currently available for CML treatment. These drugs are able to generate eight year CML-specific overall survival rates >90%, only a minority of patients will achieve molecular responses compatible with drug discontinuation. Thus, there is an unmet need for additional therapeutic targets that may lead to the cure of most patients diagnosed with CML. A growing body of evidence has suggested a role for both IRF4 and IRF8 in the pathogenesis of CML. Furthermore, IRF1 is consistently deleted at one or both alleles in patients with leukemia and myelodysplasia. Finally, we have recently demonstrated that IRF5 is a target of BCR-ABL kinase activity and reduces CML cell proliferation. In this article, we provide an update on the current knowledge of the role of the IRFs in CML.
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PMID:Roles of Interferon Regulatory Factors in Chronic Myeloid Leukemia. 2672 39

Genomic analysis has greatly influenced the diagnosis and clinical management of patients affected by diverse forms of hematologic malignancies. Here, we review how genetic alterations define subclasses of patients with acute leukemias, myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPNs), non-Hodgkin lymphomas, and classical Hodgkin lymphoma. These include new subtypes of acute myeloid leukemia defined by mutations in RUNX1 or BCR-ABL1 translocations as well as a constellation of somatic structural DNA alterations in acute lymphoblastic leukemia. Among patients with MDS, detection of mutations in SF3B1 define a subgroup of patients with the ring sideroblast form of MDS and a favorable prognosis. For patients with MPNs, detection of the BCR-ABL1 fusion delineates chronic myeloid leukemia from classic BCR-ABL1- MPNs, which are largely defined by mutations in JAK2, CALR, or MPL In the B-cell lymphomas, detection of characteristic rearrangements involving MYC in Burkitt lymphoma, BCL2 in follicular lymphoma, and MYC/BCL2/BCL6 in high-grade B-cell lymphomas are essential for diagnosis. In T-cell lymphomas, anaplastic large-cell lymphoma is defined by mutually exclusive rearrangements of ALK, DUSP22/IRF4, and TP63 Genetic alterations affecting TP53 and the mutational status of the immunoglobulin heavy-chain variable region are important in clinical management of chronic lymphocytic leukemia. Additionally, detection of BRAFV600E mutations is helpful in the diagnosis of classical hairy cell leukemia and a number of histiocytic neoplasms. Numerous additional examples provided here demonstrate how clinical evaluation of genomic alterations have refined classification of myeloid neoplasms and major forms of lymphomas arising from B, T, or natural killer cells.
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PMID:Diagnosis and classification of hematologic malignancies on the basis of genetics. 2860 Mar 36

Myelodysplastic syndrome (MDS) is a heterogeneous hematologic malignancy derived from hematopoietic stem cells and the molecular mechanism of MDS remains unclear. This study aimed to elucidate potential markers of diagnosis and prognosis of MDS. The gene expression profiles GSE19429 and GSE58831 were obtained and downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) in MDS were screened using GEO2R and overlapped DEGs were obtained with Venn Diagrams. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway functional enrichment analyses, protein-protein interaction network establishment and survival analyses were performed. Functional enrichment analysis indicated that these DEGs were significantly enriched in the interferon signaling pathway, immune response, hematopoietic cell lineage and the FOXO signaling pathway. Four hub genes and four significant modules including 25 module genes were obtained via Cytoscape MCODE. Survival analysis showed that the overall survival of MDS patients having BLNK, IRF4, IFITM1, IFIT1, ISG20, IFI44L alterations were worse than that without alterations. In conclusion, the identification of these genes and pathways helps understand the underlying molecular mechanisms of MDS and provides candidate targets for the diagnosis and prognosis of MDS.
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PMID:Screening and identification of key candidate genes and pathways in myelodysplastic syndrome by bioinformatic analysis. 3180 41