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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During the past years, several independent laboratories have highlighted the presence of nuclear signaling pathways based on lipid hydrolysis, which are not a mere duplication of those occurring at the plasma membrane. Among the enzymes of the cycle, nuclear phosphoinositide-specific phospholipase C (PI-PLC) has been analyzed quite extensively. In this context, PI-PLCbeta1 appears to play a key role as a check point in the G1 phase of the cell cycle. It has also been shown that its activation and/or up-regulation is upon the control of type 1 insulin-like growth factor receptor (IGF-R) in both mouse fibroblast and myoblasts, suggesting that its signaling activity is essential for the normal behavior of the cell, at least in culture. The recent discovery of a possible involvement of the deletion of PI-PLCbeta1 gene in the progression of myelodysplastic syndrome (MDS) to acute myeloid leukemia (AML) in humans strengthens the contention that nuclear PI-PLC signaling is essential for physiological processes such as cell growth and differentiation. Even though PI-PLCbeta1 is present and does not translocate to eukaryotic nuclei, this organelle, even though only in some conditions contains also PI-PLCgamma1 which acts not only as a PI-PLC but also as guanine nucleotide exchange factor (GEF) for PI 3-kinase enhancer (PIKE) and is somehow linked to PI 3-kinase (PI3K) activity. Also members of PI-PLCdelta family are shuttling from the nucleus to the cytoplasm and return and are possibly involved in the control of cell growth. We must also take into account the presence in the nucleus of other phospholipases such as phospholipase A2 (PLA2) and phospholipase D (PLD), which also exert a signaling activity upon external stimuli. On the whole this review highlights the latest development in the PI-PLC cycle in the nucleus, which in terms of activation, regulation and down-stream targets differs substantially from that located at the plasma membrane.
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PMID:Nuclear phospholipase C: involvement in signal transduction. 1589 48

Myelodysplastic syndromes (MDS) are defined as clonal hematopoietic stem-cell disorders characterized by ineffective hematopoiesis in one or more of the lineages of the bone marrow. Although distinct morphologic subgroups exist, the natural history of MDS is progression to acute myeloid leukemia (AML). However, the molecular the mechanisms the underlying MDS evolution to AML are not completely understood. Inositides are key cellular second messengers with well-established roles in signal transduction pathways, and nuclear metabolism elicited by phosphoinositide-specific phospholipase C (PI-PLC) beta1 and Akt plays an important role in the control of the balance between cell cycle progression and apoptosis in both normal and pathologic conditions. Recent findings evidenced the role played by nuclear lipid signaling pathways, which could become promising therapeutic targets in MDS. This review will provide a concise and updated revision of the state of art on this topic.
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PMID:Nuclear inositide signaling in myelodysplastic syndromes. 2005 33

The nuclear inositol lipid cycle is a well known process, and nuclear phosphoinositide-specific phospholipase C beta1 (PLCbeta1) signalling activity has been extensively studied in the last decades. We now know that nuclear PLCbeta1 is a key player in the control of cell cycle progression; in fact it appears to be involved in the cyclin-mediated regulation of the physiological machinery. Indeed, the recent discovery of a possible involvement of the interstitial deletion of PLCbeta1 gene in the progression of myelodysplastic syndrome (MDS) to acute myeloid leukemia in humans (AML) strengthens this contention. Albeit several papers have reported the techniques used for the study of inositide-dependent signaling in the nucleus, we describe here step by step protocols, which can be followed for the preparation of highly purified nuclei and the subsequent analysis of nuclear PLCbeta1 signaling. The described techniques range from nuclear purification to enzymatic activity and to molecular biology methods.
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PMID:Phosphoinositide-specific phospholipase C beta1 signal transduction in the nucleus. 2064 87