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|Ref Type||Journal Article|
|Authors||Gangat N, Patnaik MM, Tefferi A|
|Title||Myelodysplastic syndromes: Contemporary review and how we treat.|
|Journal||American journal of hematology|
|Abstract Text||Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell disorders with an inherent tendency for leukemic transformation. Diagnosis is currently based on the presence of peripheral blood cytopenias, peripheral blood and bone marrow dysplasia/blasts, and clonal cytogenetic abnormalities. With the advent of next generation sequencing, recurrent somatic mutations in genes involved in epigenetic regulation (TET2, ASXL1, EZH2, DNMT3A, IDH1/2), RNA splicing (SF3B1, SRSF2, U2AF1, ZRSR2), DNA damage response (TP53), transcriptional regulation (RUNX1, BCOR, ETV6) and signal transduction (CBL, NRAS, JAK2) have been identified in MDS. Conventional prognostication is by the revised International prognostic scoring system (IPSS-R) with additional adverse prognosis conferred by presence of ASXL1, EZH2, or TP53 mutations. Currently Food and Drug administration (FDA)-approved drugs for the treatment of MDS are not curative and their effect on survival is limited; they include the hypomethylating agents (HMA) azacitidine and decitabine and lenalidomide for MDS with isolated del(5q). To date, allogeneic stem cell transplant (ASCT) remains the only treatment option for possible cure. Given the current lack of drugs with convincing evidence of favorable effect on survival, we consider ASCT as the treatment of choice for most patients with symptomatic disease, and especially for those with high-risk disease. For nontransplant candidates, participation in clinical trials is preferred over conventional therapy. There is not one right way of treatment for patients who are not candidates for either ASCT or clinical trials and palliative drugs of choice depend on the clinical problem, such as symptomatic anemia (ESAs, danazol, HMA), thrombocytopenia (HMA), or neutropenia (myeloid growth factors). Conversely, there is no controlled evidence to support the use of iron chelating agents in MDS. Going forward, we believe it is time to incorporate mutation information in clinically derived prognostic models in MDS and encourage development of novel drugs with disease-modifying activity.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|ZRSR2||NCBI||U2AF1-RS2|U2AF1L2|U2AF1RS2|URP|ZC3H22||ZRSR2, zinc finger CCCH-type, RNA binding motif and serine/arginine rich 2, is a component of the splicesome that functions in 3' splice site recognition, therefore regulates expression of E2F transcription factors and genes in the Mapk/Erk pathways (PMID: 21041408, PMID: 25586593). ZRSR2 mutations are associated with myelodysplastic syndromes and acute myeloid leukemia, particularly in males (PMID: 21909114, PMID: 26769228).||Tumor suppressor|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|ETV6 mutant||myelodysplastic syndrome||not applicable||N/A||Clinical Study||Prognostic||In multiple clinical studies, ETV6 mutations were associated with a shorter overall survival in patients with myelodysplastic syndrome (PMID: 21714648, PMID: 21877899, PMID: 26769228).||21877899 26769228 21714648|
|SRSF2 mutant||myelodysplastic syndrome||not applicable||N/A||Clinical Study||Prognostic||In multiple clinical studies, SRSF2 mutations were associated with shortened survival in patients with myelodysplastic syndrome (PMID: 26769228, PMID: 26508027).||26508027 26769228|