@article{DimopoulosWeiselSongetal.2015,
  author    = {Dimopoulos, Meletios A. and Weisel, Katja C. and Song, Kevin W. and Delforge, Michel and Karlin, Lionel and Goldschmidt, Hartmut and Moreau, Philippe and Banos, Anne and Oriol, Albert and Garderet, Laurent and Cavo, Michele and Ivanova, Valentina and Alegre, Adrian and Martinez-Lopez, Joaquin and Chen, Christine and Spencer, Andrew and Knop, Stefan and Bahlis, Nizar J. and Renner, Christoph and Yu, Xin and Hong, Kevin and Sternas, Lars and Jacques, Christian and Zaki, Mohamed H. and San Miguel, Jesus F.},
  title     = {Cytogenetics and long-term survival of patients with refractory or relapsed and refractory multiple myeloma treated with pomalidomide and low-dose dexamethasone},
  series = {Haematologica},
  volume    = {100},
  journal   = {Haematologica},
  number    = {10},
  doi       = {10.3324/haematol.2014.117077},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-140349},
  pages     = {1327 -- 1333},
  year      = {2015},
  abstract  = {Patients with refractory or relapsed and refractory multiple myeloma who no longer receive benefit from novel agents have limited treatment options and short expected survival. del(17p) and t(4;14) are correlated with shortened survival. The phase 3 MM-003 trial demonstrated significant progression-free and overall survival benefits from treatment with pomalidomide plus low-dose dexamethasone compared to high-dose dexamethasone among patients in whom bortezomib and lenalidomide treatment had failed. At an updated median follow-up of 15.4 months, the progression-free survival was 4.0 versus 1.9 months (HR, 0.50; P<0.001), and median overall survival was 13.1 versus 8.1 months (HR, 0.72; P=0.009). Pomalidomide plus low-dose dexamethasone, compared with high-dose dexamethasone, improved progression-free survival in patients with del(17p) (4.6 versus 1.1 months; HR, 0.34; P < 0.001), t(4;14) (2.8 versus 1.9 months; HR, 0.49; P=0.028), and in standard-risk patients (4.2 versus 2.3 months; HR, 0.55; P<0.001). Although the majority of patients treated with high-dose dexamethasone took pomalidomide after discontinuation, the overall survival of patients treated with pomalidomide plus low-dose dexamethasone or highdose dexamethasone was 12.6 versus 7.7 months (HR, 0.45; P=0.008) in patients with del(17p), 7.5 versus 4.9 months (HR, 1.12; P=0.761) in those with t(4;14), and 14.0 versus 9.0 months (HR, 0.85; P=0.380) in standard-risk subjects. The overall response rate was higher in patients treated with pomalidomide plus low-dose dexamethasone than in those treated with high-dose dexamethasone both among standard-risk patients (35.2\% versus 9.7\%) and those with del(17p) (31.8\% versus 4.3\%), whereas it was similar in patients with t(4; 14) (15.9\% versus 13.3\%). The safety of pomalidomide plus low-dose dexamethasone was consistent with initial reports. In conclusion, pomalidomide plus low-dose dexamethasone is efficacious in patients with relapsed/refractory multiple myeloma and del(17p) and/or t(4;14).},
  language  = {en}
}
@article{RuizHerediaSanchezVegaOnechaetal.2018,
  author    = {Ruiz-Heredia, Yanira and S{\´a}nchez-Vega, Beatriz and Onecha, Esther and Barrio, Santiago and Alonso, Rafael and Carlos Mart{\´i}nez-Avila, Jose and Cuenca, Isabel and Agirre, Xabier and Braggio, Esteban and Hern{\´a}ndez, Miguel-T. and Mart{\´i}nez, Rafael and Rosi{\~n}ol, Laura and Gutierrez, Norma and Martin-Ramos, Marisa and Ocio, Enrique M. and Echeveste, Mar{\´i}a-Asunci{\´o}n and P{\´e}rez de Oteyza, Jaime and Oriol, Albert and Bargay, Joan and Gironella, Mercedes and Ayala, Rosa and Blad{\´e}, Joan and Mateos, Mar{\´i}a-Victoria and Kortum, Klaus M. and Stewart, Keith and Garc{\´i}a-Sanz, Ram{\´o}n and San Miguel, Jes{\´u}s and Jos{\´e} Lahuerta, Juan and Martinez-Lopez, Joaqu{\´i}n},
  title     = {Mutational screening of newly diagnosed multiple myeloma patients by deep targeted sequencing},
  series = {Haematologica},
  volume    = {103},
  journal   = {Haematologica},
  number    = {11},
  doi       = {10.3324/haematol.2018.188839},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227151},
  pages     = {e544-e548},
  year      = {2018},
  abstract  = {no abstract available},
  language  = {en}
}
@article{HaertleBuenacheCuestaHernandezetal.2023,
  author    = {Haertle, Larissa and Buenache, Natalia and Cuesta Hern{\´a}ndez, Hip{\´o}lito Nicol{\´a}s and Simicek, Michal and Snaurova, Renata and Rapado, Inmaculada and Martinez, Nerea and L{\´o}pez-Mu{\~n}oz, Nieves and S{\´a}nchez-Pina, Jos{\´e} Mar{\´i}a and Munawar, Umair and Han, Seungbin and Ruiz-Heredia, Yanira and Colmenares, Rafael and Gallardo, Miguel and Sanchez-Beato, Margarita and Piris, Miguel Angel and Samur, Mehmet Kemal and Munshi, Nikhil C. and Ayala, Rosa and Kort{\"u}m, Klaus Martin and Barrio, Santiago and Mart{\´i}nez-L{\´o}pez, Joaqu{\´i}n},
  title     = {Genetic alterations in members of the proteasome 26S subunit, AAA-ATPase (PSMC) gene family in the light of proteasome inhibitor resistance in multiple myeloma},
  series = {Cancers},
  volume    = {15},
  journal   = {Cancers},
  number    = {2},
  issn      = {2072-6694},
  doi       = {10.3390/cancers15020532},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305013},
  year      = {2023},
  abstract  = {For the treatment of Multiple Myeloma, proteasome inhibitors are highly efficient and widely used, but resistance is a major obstacle to successful therapy. Several underlying mechanisms have been proposed but were only reported for a minority of resistant patients. The proteasome is a large and complex machinery. Here, we focus on the AAA ATPases of the 19S proteasome regulator (PSMC1-6) and their implication in PI resistance. As an example of cancer evolution and the acquisition of resistance, we conducted an in-depth analysis of an index patient by applying FISH, WES, and immunoglobulin-rearrangement sequencing in serial samples, starting from MGUS to newly diagnosed Multiple Myeloma to a PI-resistant relapse. The WES analysis uncovered an acquired PSMC2 Y429S mutation at the relapse after intensive bortezomib-containing therapy, which was functionally confirmed to mediate PI resistance. A meta-analysis comprising 1499 newly diagnosed and 447 progressed patients revealed a total of 36 SNVs over all six PSMC genes that were structurally accumulated in regulatory sites for activity such as the ADP/ATP binding pocket. Other alterations impact the interaction between different PSMC subunits or the intrinsic conformation of an individual subunit, consequently affecting the folding and function of the complex. Interestingly, several mutations were clustered in the central channel of the ATPase ring, where the unfolded substrates enter the 20S core. Our results indicate that PSMC SNVs play a role in PI resistance in MM.},
  language  = {en}
}