Myeloma Genomics and Epigenomics
The molecular make up of smoldering myeloma highlights the evolutionary pathways leading to multiple myeloma. Boyle EM, Deshpande S, Tytarenko R, Ashby C, Wang Y, Bauer MA, Johnson SK, Wardell CP, Thanendrarajan S, Zangari M, Facon T, Dumontet C, Barlogie B, Arbini A, Rustad EH, Maura F, Landgren O, Zhan F, van Rhee F, Schinke C, Davies FE, Morgan GJ, Walker BA. Nat Commun. 2021 Jan 12;12(1):293. doi: 10.1038/s41467-020-20524-2.PMID: 33436579
Copy number signatures predict chromothripsis and clinical outcomes in newly diagnosed multiple myeloma. Maclachlan KH, Rustad EH, Derkach A, Zheng-Lin B, Yellapantula V, Diamond B, Hultcrantz M, Ziccheddu B, Boyle EM, Blaney P, Bolli N, Zhang Y, Dogan A, Lesokhin AM, Morgan GJ, Landgren O, Maura F. Nat Commun. 2021 Aug 27;12(1):5172. doi: 10.1038/s41467-021-25469-8.PMID: 34453055
Chromatin-based, in cis and in trans regulatory rewiring underpins distinct oncogenic transcriptomes in multiple myeloma. Alvarez-Benayas J, Trasanidis N, Katsarou A, Ponnusamy K, Chaidos A, May PC, Xiao X, Bua M, Atta M, Roberts IAG, Auner HW, Hatjiharissi E, Papaioannou M, Caputo VS, Sudbery IM, Karadimitris A. Nat Commun. 2021 Sep 14;12(1):5450. doi: 10.1038/s41467-021-25704-2.PMID: 34521827
Mutation landscape of multiple myeloma measurable residual disease: identification of targets for precision medicine. Zátopková M, Ševčíková T, Fanfani V, Chyra Z, Rihova L, Bezdekova R, Žihala D, Growková K, Filipova J, Černá L, Broskevičová L, Kryukov F, Minařík J, Smejkalová J, Maisnar V, Harvanová L, Pour L, Jungova A, Popková T, Bago JR, Anilkumar Sithara A, Hrdinka M, Jelinek T, Šimíček M, Stracquadanio G, Hajek R. Blood Adv. 2021 Sep 9:bloodadvances.2020003876. doi: 10.1182/bloodadvances.2020003876.
Functional Impact of Genomic Complexity on the Transcriptome of Multiple Myeloma. Ziccheddu B, Da Vià MC, Lionetti M, Maeda A, Morlupi S, Dugo M, Todoerti K, Oliva S, D’Agostino M, Corradini P, Landgren O, Iorio F, Pettine L, Pompa A, Manzoni M, Baldini L, Neri A, Maura F, Bolli N. Clin Cancer Res. 2021 Sep 15. doi: 10.1158/1078-0432.CCR-20-4366. Online ahead of print.PMID: 34526359
The Myeloma microenvironment and Bone disease
DKK1 activates noncanonical NF-kappaB signaling via IL-6-induced CKAP4 receptor in multiple myeloma. Li X, Wang J, Zhu S, Zheng J, Xie Y, Jiang H, Guo J, Wang Y, Peng Z, Wang M, Wang J, Wang S, Zhong Y, Liu Z. Blood Adv. 2021 Sep 28;5(18):3656-3667. doi:10.1182/bloodadvances.2021004315. PMID: 34470047
Tissue–resident macrophages promote early dissemination of multiple myeloma via IL-6 and TNFalpha. Akhmetzyanova I, Aaron T, Galbo P, Tikhonova A, Dolgalev I, Tanaka M, Aifantis I, Zheng D, Zang X, Fooksman D. Blood Adv. 2021 Sep 28;5(18):3592-3608. doi: 10.1182/bloodadvances.2021005327.PMID: 34550328
Circulating cytokines present in multiple myeloma patients inhibit the osteoblastic differentiation of adipose stem cells. Kobari L, Auclair M, Piau O, Ferrand N, Zaoui M, Delhommeau F, Fève B, Sabbah M, Garderet L. Leukemia. 2021 Sep 23. doi: 10.1038/s41375-021-01428-6. Online ahead of print.PMID: 34556797
Targeting Notch Inhibitors to the Myeloma Bone Marrow Niche Decreases Tumor Growth and Bone Destruction without Gut Toxicity. Sabol HM, Ferrari AJ, Adhikari M, Amorim T, McAndrews K, Anderson J, Vigolo M, Lehal R, Cregor M, Khan S, Cuevas PL, Helms JA, Kurihara N, Srinivasan V, Ebetino FH, Boeckman RK Jr, Roodman GD, Bellido T, Delgado-Calle J. Cancer Res. 2021 Oct 1;81(19):5102-5114. doi: 10.1158/0008-5472.CAN-21-0524. Epub 2021 Aug 4.PMID: 34348968
The Myeloma Immune System
Humoral immune reconstitution after anti-BCMA CAR-T cell therapy in relapse/refractory multiple myeloma. Wang Y, Li C, Xia J, Li P, Cao J, Pan B, Tan X, Li H, Qi K, Wang X, Shi M, Jing G, Yan Z, Cheng H, Zhu F, Sun H, Sang W, Li D, Zhang X, Li Z, Zheng J, Liang A, Zhou J, Xu K. Blood Adv. 2021 Sep 29:bloodadvances.2021004603. doi: 10.1182/bloodadvances.2021004603.
Transient regulatory T–cell targeting triggers immune control of multiple myeloma and prevents disease progression. Dahlhoff J, Manz H, Steinfatt T, Delgado-Tascon J, Seebacher E, Schneider T, Wilnit A, Mokhtari Z, Tabares P, Böckle D, Rasche L, Martin Kortüm K, Lutz MB, Einsele H, Brandl A, Beilhack A. Leukemia. 2021 Sep 28. doi: 10.1038/s41375-021-01422-y.
Entinostat induces antitumor immune responses through immune editing of tumor neoantigens. Truong AS, Zhou M, Krishnan B, Utsumi T, Manocha U, Stewart KG, Beck W, Rose TL, Milowsky MI, He X, Smith CC, Bixby LM, Perou CM, Wobker SE, Bailey ST, Vincent BG, Kim WY. J Clin Invest. 2021 Aug 16;131(16):e138560. doi: 10.1172/JCI138560.
Intron retention–induced neoantigen load correlates with unfavorable prognosis in multiple myeloma. Dong C, Cesarano A, Bombaci G, Reiter JL, Yu CY, Wang Y, Jiang Z, Zaid MA, Huang K, Lu X, Walker BA, Perna F, Liu Y.Oncogene. 2021 Oct;40(42):6130-6138. doi: 10.1038/s41388-021-02005-y. Epub 2021 Sep 9.
Clonal hematopoiesis in patients receiving chimeric antigen receptor T-cell therapy. Miller PG, Sperling AS, Brea EJ, Leick MB, Fell GG, Jan M, Gohil SH, Tai YT, Munshi NC, Wu CJ, Neuberg DS, Maus MV, Jacobson C, Gibson CJ, Ebert BL. Blood Adv. 2021 Aug 10;5(15):2982-2986. doi: 10.1182/bloodadvances.2021004554.
Molecular mechanisms of Drug Resistance and/or Sensitivity
RARgamma activation sensitizes human myeloma cells to carfilzomib treatment through OAS-RNase L innate immune pathway. Wang Q, Lin Z, Wang Z, Ye L, Xian M, Xiao L, Su P, Bi E, Huang YH, Qian J, Liu L, Ma X, Yang M, Xiong W, Zu Y, Pingali SR, Xu B, Yi Q. Blood. 2021 Aug 19:blood.2020009856. doi: 10.1182/blood.2020009856.
Heterogeneous modulation of Bcl–2 family members and drug efflux mediate MCL-1 inhibitor resistance in multiple myeloma. Bolomsky A, Miettinen JJ, Malyutina A, Besse A, Huber J, Fellinger S, Breid H, Parsons A, Klavins K, Hannich JT, Kubicek S, Caers J, Hübl W, Schreder M, Zojer N, Driessen C, Tang J, Besse L, Heckman CA, Ludwig H. Blood Adv. 2021 Oct 26;5(20):4125-4139. doi: 10.1182/bloodadvances.2020003826.
Single–Cell Profiling Reveals Metabolic Reprogramming as a Resistance Mechanism in BRAF-Mutated Multiple Myeloma. Waldschmidt JM, Kloeber JA, Anand P, Frede J, Kokkalis A, Dimitrova V, Potdar S, Nair MS, Vijaykumar T, Im NG, Guillaumet-Adkins A, Chopra N, Stuart H, Budano L, Sotudeh N, Guo G, Grassberger C, Yee AJ, Laubach JP, Richardson PG, Anderson KC, Raje NS, Knoechel B, Lohr JG. Clin Cancer Res. 2021 Sep 13. doi: 10.1158/1078-0432.CCR-21-2040.
Novel Targets & Therapeutics
IAP and HDAC inhibitors interact synergistically in myeloma cells through noncanonical NF-kappaB- and caspase-8-dependent mechanisms. Zhou L, Zhang Y, Meads MB, Dai Y, Ning Y, Hu X, Li L, Sharma K, Nkwocha J, Parker R, Bui D, McCarter J, Kramer L, Purcell C, Sudalagunta PR, Canevarolo RR, Coelho Siqueira Silva MD, De Avila G, Alugubelli RR, Silva AS, Kmeiciak M, Ferreira-Gonzalez A, Shain KH, Grant S. Blood Adv. 2021 Oct 12;5(19):3776-3788. doi: 10.1182/bloodadvances.2020003597.
BCMA–Specific ADC MEDI2228 and Daratumumab Induce Synergistic Myeloma Cytotoxicity via IFN-Driven Immune Responses and Enhanced CD38 Expression. Xing L, Wang S, Liu J, Yu T, Chen H, Wen K, Li Y, Lin L, Hsieh PA, Cho SF, An G, Qiu L, Kinneer K, Munshi N, Anderson KC, Tai YT. Clin Cancer Res. 2021 Jul 23. doi: 10.1158/1078-0432.CCR-21-1621.
Treatment with HIV–Protease Inhibitor Nelfinavir Identifies Membrane Lipid Composition and Fluidity as a Therapeutic Target in Advanced Multiple Myeloma. Besse L, Besse A, Stolze SC, Sobh A, Zaal EA, van der Ham AJ, Ruiz M, Phuyal S, Büchler L, Sathianathan M, Florea BI, Borén J, Ståhlman M, Huber J, Bolomsky A, Ludwig H, Hannich JT, Loguinov A, Everts B, Berkers CR, Pilon M, Farhan H, Vulpe CD, Overkleeft HS, Driessen C. Cancer Res. 2021 Sep 1;81(17):4581-4593. doi: 10.1158/0008-5472.CAN-20-3323. Epub 2021 Jun 22.
