The mechanistic role of epigenetic in multiple myeloma

This article reviews recent findings on the role of epigenetic alterations in MM pathogenesis, which affect the expression of cell cycle regulatory molecules, apoptosis, DNA repair system, CD markers, cell signaling pathways as well as tumor suppressor miRNAs. Given these results, it can be stated that these epigenetic changes play an important role in the initiation and progression of MM. Therefore, understanding the impact of epigenetics in MM pathogenesis in each stage of disease progression can help develop therapeutic targets to increase survival and reduce drug resistance.
Source: Comparative Clinical Pathology - Category: Pathology Source Type: research

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Abstract Therapeutic strategies designed to tinker with cancer cell DNA damage response have led to the widespread use of PARP inhibitors for BRCA1/2-mutated cancers. In the haematological cancer multiple myeloma, we sought to identify analogous synthetic lethality mechanisms that could be leveraged upon established cancer treatments. The combination of ATR inhibition using the compound VX-970 with a drug eliciting interstrand cross-links, melphalan, was tested in in vitro, ex vivo, and most notably in vivo models. Cell proliferation, induction of apoptosis, tumor growth and animal survival were assessed. The comb...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
CONCLUSIONWhen detecting a lytic spinal tumor in a patient who suffers from LS a SPB should be taken under consideration.
Source: International Journal of Surgery Case Reports - Category: Surgery Source Type: research
In conclusion, our findings link the calcification of the vascular tissue with the expression of FGF23 in the vessels and with the elevation of circulating levels this hormone. Permanently Boosting Levels of Natural Killer Cells in Mice to Increase Cancer Resistance https://www.fightaging.org/archives/2019/09/permanently-boosting-levels-of-natural-killer-cells-in-mice-to-increase-cancer-resistance/ Researchers here demonstrate a very interesting approach to immunotherapy: they introduce engineered stem cells in mice that will give rise to additional natural killer T cells, boosting the capability of the ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Multiple myeloma (MM) is a hematological malignancy of B cells, characterized by clonal proliferation of malignant plasma cells. DNA damage and genomic instability play an important role in the pathogenesis of MM. Based on the characteristics of high heterogeneity and genomic instability of MM, and the protective effect of M Φs on MM cells (MMCs), our study intended to further clarify whether MΦs affect MMCs DNA damage response and DNA repair, and the relationship between MΦs and genomic instability of MMCs.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Source Type: research
Mutational characterisation is described in newly diagnosed (ND) multiple myeloma (MM) but remains largely elusive for relapsed/refractory (RR) patients. Current practice for mutational characterisation is via analysis of DNA from single-site bone marrow (BM) biopsies, which is confounded by the known inter and intra-clonal spatial heterogeneity of the tumour(s). An alternative and more comprehensive approach is through the analysis of circulating cell-free (cf) tumour DNA (ctDNA) derived from the plasma (PL).
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Source Type: research
A hallmark of myeloma is high level production of immunoglobulins leading to a heavy load on protein folding and homeostasis in tumor cells. The aminopeptidase gene family catalyze the hydrolysis of amino acid residues from proteins or peptides and are last in line for protein degradation. They are thus an important group of metalloenzymes implicated in cellular functions such as differentiation, cell cycle, DNA repair, and apoptosis. Since aminopeptidases operate downstream of the ubiquitin-proteasome pathway, enzymatic activity of these proteases can be utilized by peptide conjugated drugs.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Source Type: research
Recurrent chromosomal aberrations are the main hallmark of multiple myeloma (MM). A recent large scale genome-wide analysis has unveiled that the co-occurrence of 17p13(del) and 1q21(amp) lesions constitute a novel high-risk disease group. Within 17p13, lies TP53 that maintains the genomic integrity by keeping the double stranded DNA damage (DSB) pathway in check. On the other hand, ADAR1 is a critical gene within 1q21 and we have recently reported that its direct RNA editing mechanism on NEIL1 (base-excision repair (BER) gene) caused defective single stranded DNA breaks (SSB) repair, resulting in CHK1 activation.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Source Type: research
In this study, we show that CASIN, a selective inhibitor of cell division cycle 42 (Cdc42) GTPase, inhibited proliferation and survival of melphalan/bortezomib-resistant MM cells more profoundly than that of the sensitive cells. Furthermore, CASIN was more potent than melphalan/bortezomib in inhibiting melphalan/bortezomib-resistant cells. In addition, CASIN sensitized melphalan/bortezomib-resistant cells to this drug combination. Mechanistically, Cdc42 activity was higher in melphalan/bortezomib-resistant cells than that in the sensitive cells. CASIN inhibited mono-ubiquitination of Fanconi anemia (FA) complementation gro...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In previous studies of recurrently amplified 1q21 genes in multiple myeloma (MM), we identified ILF2 (Interleukin Enhancer Binding Factor 2) as a key modulator of the DNA repair pathway, which promotes adaptive responses to genotoxic stress in a dose-dependent manner, explaining why 1q21 patients benefit less from high-dose chemotherapy than non-1q21 patients do (Cancer Cell 2017). These findings prompted us to develop strategies for blocking ILF2 signaling to enhance the effectiveness of available DNA-damaging agent-based treatments.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Source Type: research
Researchers here demonstrate a very interesting approach to immunotherapy: they introduce engineered stem cells in mice that will give rise to additional natural killer T cells, boosting the capability of the immune system for the entire life span of the mouse. Even if this class of treatment is not actually permanent in the same way in humans, and merely long-lasting, it still seems a promising step towards enhancing the immune system at any age, not just trying to repair it when it fails in later life. They've been called the "special forces" of the immune system: invariant natural killer T cells. Alth...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
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