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)

Lymphoblastic lymphoma is the second most common type of non-Hodgkin lymphoma seen in children. Approximately, 90% of lymphoblastic lymphomas arise from T cells, with the remaining 10% being B-cell-lineage derived. Although T-cell lymphoblastic lymphoma most frequently occurs in the anterior mediastinum (thymus), B-cell lymphoblastic lymphoma (B-LBL) predominates in extranodal sites such as skin and bone. Here, we describe a pediatric B-LBL patient who presented with extensive abdominal involvement and whose lymphoma cells displayed segmental duplication of the mixed lineage leukemia (MLL) gene. MLL duplication/amplification has been described primarily in acute myeloid leukemia and myelodysplastic syndrome with no published reports of discrete MLL duplication/amplification events in B-LBL. The MLL gene duplication noted in this case may represent a novel mechanism for tumorigenesis in B-LBL.
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PMID:MLL duplication in a pediatric patient with B-cell lymphoblastic lymphoma. 2205 66

Previous epigenetics research in myelodysplastic syndromes (MDS) mainly focused on the DNA methylation of tumor suppressor genes. Recent studies reported that around 6% of MDS patients have several EZH2 mutations including missense, frameshift and truncated mutations. Histone methyltransferase EZH2 plays a critical role in epigenetic regulation as a bridge between histone methylation/deacetylation and DNA methylation. EZH2 is frequently overexpressed and considered to be an oncogene in cancers; nevertheless, EZH2 is considered as a candidate tumor suppressor gene in MDS due to EZH2 mutations associated with poor survival. Many questions still need further discussion. Moreover, 3-deazaneplanocin can reduce EZH2 levels and H3K27 trimethylation, and synergistic effects are seen in combination with DNA demethylation agents or histone deacetylation inhibitors. All of the above give us more chances to improve epigenetic therapy in MDS. Therefore, the molecular mechanisms of EZH2 in tumorigenesis and the role of EZH2 in MDS are studied.
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PMID:The role of histone methyltransferase EZH2 in myelodysplastic syndromes. 2247 86

Leukemias including acute myeloid leukemia (AML), acute lymphocytic leukemia, and chronic myeloid leukemia as well as myelodysplastic syndrome (MDS), male non-Hodgkin lymphoma and MGUS are statistically significant radiation-associated hematopoietic neoplasms. Recently, MDS has been confirmed to increase among atomic bomb survivors. AML/RUNX1 is a critical transcription factor of differentiation and proliferation of hematopoietic stem cells. AML1 point mutations, especially N-terminal RUNT domain in-frame type, are frequently detected in radiaton-associated and therapy-related (rad-t-) MDS/AML. In addition, the point mutations, are frequently associated with additional mutations in receptor tyrosine kinase (RTK)-RAS pathway, including FLT3, N-RAS, SHP2 and NF1. The combination of AML1/RUNX1 mutation and RTK-RAS pathway mutation in hematopoietic stem cells is considered responsible for the oncogenesis of rad-t- MDS/AML.
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PMID:[Radiation associated leukemia and myelodysplastic syndrome]. 2251 21

Ribosomes are essential components of the protein translation machinery and are composed of more than 80 unique large and small ribosomal proteins. Recent studies show that in addition to their roles in protein translation, ribosomal proteins are also involved in extra-ribosomal functions of DNA repair, apoptosis and cellular homeostasis. Consequently, alterations in the synthesis or functioning of ribosomal proteins can lead to various hematologic disorders. These include congenital anemias such as Diamond Blackfan anemia and Shwachman Diamond syndrome; both of which are associated with mutations in various ribosomal genes. Acquired uniallelic deletion of RPS14 gene has also been shown to lead to the 5q syndrome, a distinct subset of MDS associated with macrocytic anemia. Recent evidence shows that specific ribosomal proteins are overexpressed in liver, colon, prostate and other tumors. Ribosomal protein overexpression can promote tumorigenesis by interactions with the p53 tumor suppressor pathway and also by direct effects on various oncogenes. These data point to a broad role of ribosome protein alterations in hematologic and oncologic diseases.
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PMID:Alterations in the ribosomal machinery in cancer and hematologic disorders. 2270 27

The abnormalities of SALL4 gene, which encodes a zinc-finger transcription factor and is essential for developmental events, have been found to be involved in tumorigenesis. In this study, we investigated the methylation status of the CpG island of SALL4 promoter region in myelodysplastic syndrome (MDS) using methylation-specific PCR (MSP). Aberrant hypomethylation of SALL4 gene was found in 21.7% (18/83) of the cases analyzed. A significantly positive correlation was identified between the level of SALL4 transcript and the status of SALL4 hypomethylation (R=0.641, P<0.001). No correlation was found between SALL4 hypomethylation and clinical parameters. However, the frequency of SALL4 hypomethylation significantly increased in higher risk MDS (14% in Low/Int-1 versus 39% in Int-2/High, P=0.031). The association between SALL4 hypomethylation and the mutations in three methylation modifiers (IDH1, IDH2 and DNMT3A) was not observed. Although the estimated 50% survival time of the SALL4-hypomethylated group was shorter than that of SALL4-methylated group (11.0 months vs. 20.0 months), the difference was not statistically significant (P=0.430). These findings suggest that hypomethylation of SALL4 promoter is a common event in MDS.
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PMID:Aberrant hypomethylation of SALL4 gene in patients with myelodysplastic syndrome. 2312 7

The formation of clathrin-coated vesicles is essential for intracellular membrane trafficking between subcellular compartments and is triggered by the ARF family of small GTPases. We previously identified SMAP1 as an ARF6 GTPase-activating protein that functions in clathrin-dependent endocytosis. Because abnormalities in clathrin-dependent trafficking are often associated with oncogenesis, we targeted Smap1 in mice to examine its physiological and pathological significance. Smap1-deficent mice exhibited healthy growth, but their erythroblasts showed enhanced transferrin endocytosis. In mast cells cultured in SCF, Smap1 deficiency did not affect the internalization of c-KIT but impaired the sorting of internalized c-KIT from multivesicular bodies to lysosomes, resulting in intracellular accumulation of undegraded c-KIT that was accompanied by enhanced activation of ERK and increased cell growth. Interestingly, approximately 50% of aged Smap1-deficient mice developed anemia associated with morphologically dysplastic cells of erythroid-myeloid lineage, which are hematological abnormalities similar to myelodysplastic syndrome (MDS) in humans. Furthermore, some Smap1-deficient mice developed acute myeloid leukemia (AML) of various subtypes. Collectively, to our knowledge these results provide the first evidence in a mouse model that the deregulation of clathrin-dependent membrane trafficking may be involved in the development of MDS and subsequent AML.
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PMID:Smap1 deficiency perturbs receptor trafficking and predisposes mice to myelodysplasia. 2343 93

Epigenetic research plays an important role in the malignant tumor genotyping and tumor clinical treatment recently. Epigenetics is the study of changes in gene function that are mitotically and/or meiotically heritable and that do not entail a change in DNA sequence, including DNA methylation and histone modifications. DNA methylation is one of the most important epigenetic modifications often occurring on the cytosine of CpG islands located in gene promoter regions, which is thought to be closely correlated with tumorigenesis. The inducibility and reversibility of DNA methylation provide us an insight into tumor development and treatment. Aberrant DNA hypermethylation is associated with the progress of myelodysplastic syndrome (MDS). The DNA methyltransferase inhibitors (azacytidine and decitabine) have achieved suc-cess in treating high-and intermediate-risk MDS. This will bring new ideas to understand the cause and develop the treat-ment of MDS. This review mainly introduces the latest progress of the action mechanism of those two medicines, the clini-cal effect and new problems during the clinical application on MDS.
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PMID:[Application of DNA methyltransferase inhibitors for myelodysplastic syndrome]. 2344 25

The myelodysplastic syndromes (MDSs) are a group of clonal stem cell disorders resulting from aberrations within hematopoietic stem cells (HSCs), which may lead to the onset of a number of diseases, including acute myeloid leukemia (AML). Recent studies have demonstrated that the expression levels of the DLK1 gene are increased in MDS. In order to determine whether the addition of DLK1 affects tumorigenesis, small interfering (si)RNAs were designed to target DLK1 in order to knockdown its expression in CD34+CD38- bone marrow cells in MDS. A lower proliferative rate was observed in the CD34+CD38- bone marrow cells following this knockdown of DLK1 expression. The suppression of DLK1 expression resulted in a less aggressive MDS phenotype, which suggests that the upregulation of DLK1 expression may play an oncogenic role in CD34+CD38- bone marrow cells.
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PMID:Effect of DLK1 on tumorigenesis in CD34+CD38- bone marrow cells in myelodysplastic syndromes. 2394 4

We describe the case of a 70-year-old male with acromegaly who developed colon carcinoma and myelodysplastic syndrome (MDS) during the course of acromegaly. MDS progressed to acute myeloid leukemia, but was refractory to chemotherapy. Acromegaly is a rare disorder caused by excessive amounts of growth hormone (GH) primarily secreted by pituitary adenomas. Patients with acromegaly are more prone to develop various malignancies, but there are few reports of hematological malignancies in such patients. In the present case, excessive endogenous GH and insulin-like growth factor-I levels may have altered cell proliferation and thereby affected the oncogenesis and chemosensitivity of both malignancies.
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PMID:Acute myeloid leukemia and colon carcinoma during the course of acromegaly. 2406 73

Mutation is a fundamental process in tumorigenesis. However, the degree to which the rate of somatic mutation varies across the human genome and the mechanistic basis underlying this variation remain to be fully elucidated. Here, we performed a cross-cancer comparison of 402 whole genomes comprising a diverse set of childhood and adult tumors, including both solid and hematopoietic malignancies. Surprisingly, we found that the inactive X chromosome of many female cancer genomes accumulates on average twice and up to four times as many somatic mutations per megabase, as compared to the individual autosomes. Whole-genome sequencing of clonally expanded hematopoietic stem/progenitor cells (HSPCs) from healthy individuals and a premalignant myelodysplastic syndrome (MDS) sample revealed no X chromosome hypermutation. Our data suggest that hypermutation of the inactive X chromosome is an early and frequent feature of tumorigenesis resulting from DNA replication stress in aberrantly proliferating cells.
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PMID:Hypermutation of the inactive X chromosome is a frequent event in cancer. 2413 98


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