Abstract
Myelodysplastic syndromes (MDS) are a heterogeneous group of hematological malignancies characterized by peripheral blood cytopenia and abnormal myeloproliferation, as well as a variable risk of evolution into acute myeloid leukemia (AML). The nucleus is a highly organized organelle with several distinct domains where nuclear inositides localize to mediate essential cellular events. Nuclear inositides play a critical role in the modulation of erythropoiesis or myelopoiesis. Here, we briefly review the nuclear structure, the localization of inositides and their metabolic enzymes in subnuclear compartments, and the molecular aspects of nuclear inositides in MDS.
Highlights
Phosphoinositides (PIs) are inositol phospholipids constituted of hydrophilic inositol groups linked to two fatty chains, which are involved in several signaling pathways
Nuclear of the presence of a phospholipid content in the nuclear chromatin were reported [29,30]. This was speckles are reservoirs of pre-messenger RNA splicing factors and other transcription regulatory an intriguing period for lipid research and it inspired a massive interest in nuclear research, leading proteins which are frequently recruited to active transcription sites [24,25], which is why genes to the discovery, in 1983, of phosphatidylinositol phosphate kinase activity in the nucleus [31] and, localizing to nuclear speckles are involved in gene expression
All these evidences reveal the role of PLCβ1/PKCα signaling in erythroid differentiation on del(5q) low-risk myelodysplastic syndromes (MDS) patients responding to lenalidomide, and opening the way to innovative targeted therapies
Summary
Phosphoinositides (PIs) are inositol phospholipids constituted of hydrophilic inositol groups linked to two fatty chains, which are involved in several signaling pathways. Phosphoinositide-specific phospholipases (PLCs) are a group of inositide-dependent enzymes that cleave phosphatidylinositol 4,5-biphosphate (PtdIns(4,5)P2) to inositol 1,4,5-trisphophate (IP3) and diacylglycerol (DAG) These are key second messengers that induce or inhibit cell proliferation, cell apoptosis, activation of immune, cells and stem cell differentiation via intracellular release of calcium ions and activation of protein kinase C (PKC), respectively [3,4] (Figure 1). Cells 2020, 9, 697 phosphatidylinositol-3-kinase (PI3K)/Akt/mTOR signaling pathway plays an important role in the control of several cellular processes, such as cell growth, proliferation, survival, and neoplastic. Dependent interactions and regulatory signals that alter several critical cellular events implicated in Recently, a molecular study has linked a few inositide-related genes to the lack of response to epigenetic. We briefly describe the nuclear signals that alter several critical cellular events implicated in MDS, such as cell proliferation or apoptosis, architecture and nuclear inositide metabolism while establishing a link between nuclear inositidearedependent still not fully understood [21].
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