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)

Bone marrow cells of patients with myelodysplastic syndromes (MDS) frequently undergo apoptosis, though the apoptotic cell ratio decreases when overt leukemia (OL) develops. Thus, we compared the expression of the inhibitor of apoptosis protein (IAP) gene family proteins in bone marrow samples from control, MDS, OL transformed from MDS (MDS --> OL), and de novo acute myelogenous leukemia (AML) subjects by the quantitative real-time RT-PCR method and an immunohistochemical approach. Overexpression of mRNA for survivin, cIAP1, NAIP and XIAP was significant in MDS bone marrow cells compared with control samples. However, the expression of mRNA for survivin, cIAP1 and cIAP2 exhibited a remarkable decrease after the development of OL (MDS --> OL). By immunohistochemistry, survivin was found to localize to the nucleus of myeloid cells in the majority of MDS cases. Next, the chronological changes in the expression of IAPs were determined in cases of MDS with evolution of OL. Although the expression of cIAP1 and cIAP2 revealed a sudden or gradual decrease as OL developed, survivin in many cases and XIAP in the majority of cases exhibited a peak of expression before a decline, indicating that these IAPs could be associated with the early events in the development of OL.
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PMID:Expression of IAP family proteins in myelodysplastic syndromes transforming to overt leukemia. 1538 Mar 46

Tumor necrosis factor (TNF)-alpha, a potent stimulus of nuclear factor-kappaB (NF-kappaB), is up-regulated in myelodysplastic syndrome (MDS). Here, we show that bone marrow mononuclear cells (BMMCs) and purified CD34+ cells from patients with low-grade/early-stage MDS (refractory anemia/refractory anemia with ring sideroblasts [RA/RARS]) have low levels of NF-kappaB activity in nuclear extracts comparable with normal marrow, while patients with RA with excess blasts (RAEB) show significantly increased levels of activity (P = .008). Exogenous TNF-alpha enhanced NF-kappaB nuclear translocation in MDS BMMCs above baseline levels. Treatment with arsenic trioxide (ATO; 2-200 microM) inhibited NF-kappaB activity in normal marrow, primary MDS, and ML1 cells, even in the presence of exogenous TNF-alpha (20 ng/mL), and down-regulated NF-kappaB-dependent antiapoptotic proteins, B-cell leukemia XL (Bcl-XL), Bcl-2, X-linked inhibitor of apoptosis (XIAP), and Fas-associated death domain (FADD)-like interleukin-1beta-converting enzyme (FLICE) inhibitory protein (FLIP), leading to apoptosis. However, overexpression of FLIP resulted in increased NF-kappaB activity and rendered ML1 cells resistant to ATO-induced apoptosis. These data are consistent with the observed up-regulation of FLIP and resistance to apoptosis with advanced MDS, where ATO as a single agent may show only limited efficacy. However, the data also suggest that combinations of ATO with agents that interfere with other pathways, such as FLIP autoamplification via NF-kappaB, may have considerable therapeutic activity.
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PMID:NF-kappaB and FLIP in arsenic trioxide (ATO)-induced apoptosis in myelodysplastic syndromes (MDSs). 1610 82

The apoptotic mode of cell death is a major regulatory process in all complex organisms. The low proliferative index and slow accumulation of malignant cells in chronic lymphocytic leukemia (CLL), the most frequent type of leukemia in Europe and North America, suggests that the disease is caused by a defect in apoptosis regulation. Classical apoptosis is executed through the activation of caspases, cysteine proteases which are regulated by a number of pro- and anti-apoptotic proteins. One such checkpoint is the control of caspase activation by a relatively new family of inhibitor of apoptosis proteins (IAPs). They block both the mitochondrial-dependent and -independent apoptotic pathways. The IAP family inhibits apoptosis by binding to specific caspases and possibly by other mechanisms. They also participate in the regulation of cellular and intracellular signal transduction. Six human IAPs have been identified: XIAP, cIAP1, cIAP2, NAIP, livin, and survivin. Because of their important role in regulating apoptosis, IAPs are being investigated as a potential prognostic factor as well as a treatment target in cancer patients. Overexpression of several IAPs has been detected in various hematological malignancies, including acute leukemias, myelodysplastic syndrome (MDS), chronic myeloid leukemia (CML), and many types of lymphoid malignancies, such as chronic lymphocytic leukemia (CLL) and diffuse large B-cell lymphoma (DLBCL). Many publications revealed significant correlation between a high level of IAPs, especially of XIAP and survivin, and tumor progression. It seems that overexpression of XIAP in acute myeloid leukemia (AML) and survivin in acute lymphoblastic leukemia (ALL) and DLBCL could become a new unfavorable prognostic factor. Many studies are now concentrating on evaluating the expression and significance of the other proteins of the IAP family. In this paper the current knowledge of the importance of IAPs in hematological malignancies is presented.
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PMID:[The role of the inhibitor of apoptosis protein (IAP) family in hematological malignancies]. 1828 36