scholarly journals The SUMOylation Pathway as a Potential Therapeutic Target in Multiple Myeloma

10.5772/31013 ◽  
2012 ◽  
Author(s):  
James J.
Keyword(s):  
Multiple Myeloma ◽  
Therapeutic Target ◽  
Potential Therapeutic Target

scholarly journals Global Genomic Analysis of Newly Diagnosed t(4 ;14) Multiple Myeloma Reveals a Specific Mutational Spectrum and Identifies PKD2 As a Potential Therapeutic Target

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4462-4462
Author(s):  
Xiu Ly Song ◽  
Raphaël Szalat ◽  
Alexis Talbot ◽  
HaiVu Nguyen ◽  
Mehmet K. Samur ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Lines ◽  
Therapeutic Target ◽  
Plasma Cells ◽  
Genomic Analysis ◽  
Sequencing Analysis ◽  
Newly Diagnosed ◽  
Potential Therapeutic Target ◽  
Mutational Landscape

Abstract In Multiple Myeloma (MM), the t(4;14) translocation is associated with a poor outcome. However, beside this translocation, the genetic events which determine the adverse evolution of the disease and the resistance to treatments remain elusive. In this study we performed whole exome or RNA sequencing analysis of samples from 65 newly diagnosed t(4;14) MM. We found that NRAS, KRAS, MAPK and FGFR3 are frequently mutated (12%, 9%, 13.8%, and 20% respectively). Overall, the FGFR3/RAS/BRAF/MAPK genes were mutated in 36 cases (54%). There was a negative correlation between mutations in FGFR3 and those occurring in NRAS, KRAS and BRAF as expected from the mutually exclusive occurrence of mutations in these genes. In addition to alterations in TP53 and DIS3, we found marked elevated frequency of mutations in PRKD2 (10.7%), ATM/ATR (10.7%) and MYCBP2 (7.6%), reduced frequency in FAM46C (1.5%) and no mutation in TRAF3 and CCND1. Mutations in ATM/ATR were strongly associated with the MB4-2 breakpoint (Bp) (p = 1.62 10-4) and significantly correlated with mutations affecting genes coding for members of the MAPK family. We observed a positive correlation between non-silent mutations in PRKD2 and the MB4-1 or MB4-3 Bp (p = 1.3 10-2). Of note, PRKD2 mutations are exclusively found in 3 t(4;14) MM cell lines and among the 84 MM sequenced by Bolli et al. (1), none of the non t(4;14) patient were mutated in PRKD2, indicating that this genetic lesion is associated with t(4;14) MM. In the NCI-H929 t(4;14) MM cell line, which is mutated for PRKD2, encoding the PKD2 serine/threonine kinase, we observed elevated levels of phosphorylated PKD2. Furthermore, inhibition of PKD, decreased PKD2 phosphorylation and triggered reduced proliferation and apoptosis of MM cell lines and fresh plasma cells from patients in vitro. These results define a specific mutational landscape for t(4;14) MM and identify PKD2 as a potential therapeutic target in MM patients. Altogether, these results define a specific mutational landscape for t(4;14) MM and identify PKD2 as a potential therapeutic target in MM patients. Reference 1. Bolli, N., Avet-Loiseau, H., Wedge, D.C., Van Loo, P., Alexandrov, L.B., Martincorena, I., Dawson, K.J., Iorio, F., Nik-Zainal, S., Bignell, G.R., et al. (2014). Heterogeneity of genomic evolution and mutational profiles in multiple myeloma. Nat Commun 5, 2997. Disclosures Munshi: Janssen: Consultancy; Takeda: Consultancy; Celgene: Consultancy; Amgen: Consultancy; Merck: Consultancy; Pfizer: Consultancy; Oncopep: Patents & Royalties.

Exosomal circRNA as a novel potential therapeutic target for multiple myeloma-related peripheral neuropathy

2021 ◽  
Vol 78 ◽  
pp. 109872
Author(s):  
Yanyu Zhang ◽  
Michael Pisano ◽  
Nianhu Li ◽  
Guoqing Tan ◽  
Fumou Sun ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Peripheral Neuropathy ◽  
Therapeutic Target ◽  
Potential Therapeutic Target

scholarly journals TRAF6 Activation in Multiple Myeloma: A Potential Therapeutic Target

2012 ◽  
Vol 12 (3) ◽  
pp. 155-163 ◽  
Author(s):  
Hong Liu ◽  
Samantha Tamashiro ◽  
Stavroula Baritaki ◽  
Manuel Penichet ◽  
Youhua Yu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Therapeutic Target ◽  
Potential Therapeutic Target

scholarly journals In reply to Schäferet al: new evidence on the role of endothelin-1 axis as a potential therapeutic target in multiple myeloma

2018 ◽  
Vol 184 (6) ◽  
pp. 1052-1055 ◽  
Author(s):  
Anna Russignan ◽  
Cecilia Spina ◽  
Nicola Tamassia ◽  
Adriana Cassaro ◽  
Antonella Rigo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Therapeutic Target ◽  
Potential Therapeutic Target ◽  
Endothelin 1 ◽  
New Evidence

scholarly journals CD26 is a potential therapeutic target by humanized monoclonal antibody for the treatment of multiple myeloma

2018 ◽  
Vol 8 (11) ◽  
Author(s):  
Hiroko Nishida ◽  
Mutsumi Hayashi ◽  
Chikao Morimoto ◽  
Michiie Sakamoto ◽  
Taketo Yamada
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibody ◽  
Therapeutic Target ◽  
Potential Therapeutic Target ◽  
Humanized Monoclonal Antibody

scholarly journals Amplification and overexpression of E2 ubiquitin conjugase UBE2T promotes homologous recombination in multiple myeloma

2019 ◽  
Vol 3 (23) ◽  
pp. 3968-3972 ◽  
Author(s):  
David A. Alagpulinsa ◽  
Subodh Kumar ◽  
Srikanth Talluri ◽  
Purushothama Nanjappa ◽  
Leutz Buon ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Homologous Recombination ◽  
Therapeutic Target ◽  
Recombination Activity ◽  
Potential Therapeutic Target ◽  
Myeloma Cells ◽  
Key Points

Key Points UBE2T is frequently amplified and/or overexpressed and is required for homologous recombination activity in multiple myeloma cells. UBE2T is a potential therapeutic target to increase chemosensitivity in multiple myeloma cells.

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