Plasma cell disorders and multiple myeloma

Plasma cells produce large amounts of proteins. Targeting aberrant mRNA networking could be a promising option for treating plasma cell disorders. We aim to discover genetic vulnerabilities that can be effectively targeted with already available compounds using CRISPR/Cas9 editing in vivo and in vitro. Our findings will be translated into preclinical studies with the use of primary patient samples and patient-derived xenografts.

The bone marrow microenvironment, comprising bone marrow stromal cells, plays a pivotal role in both the progression of diseases and the development of treatment resistance in plasma cell disorders. The aim of this project is to genetically and metabolically characterize primary bone marrow stromal cells at different disease stages and under various treatment conditions. This approach aims to analyze their role in disease progression and the development of treatment resistance.

For a full list of publications see www.scopus.com/authid/detail.uri.

Brioli A*, Nägler TM*, Yomade O, Rüthrich MM, Scholl S, Frietsch JJ, Hilgendorf I, Ernst T, Sayer HG, Hochhaus A, Mügge LO, von Lilienfeld-Toal M. Sex-disaggregated analysis of biology, treatment tolerability and outcome of Multiple Myeloma in a German cohort. Oncol Res Treat 2022; 45(9): 494-503
*equal contribution

Schütt J, Nägler T, Schenk T, Brioli A. Investigating the Interplay between Myeloma Cells and Bone Marrow Stromal Cells in the Development of Drug Resistance: Dissecting the Role of Epigenetic Modifications. Cancers (Basel) 2021;13(16):4069.

Brioli A, Vom Hofe F, Rucci P, Ernst T, Yomade O, Hilgendorf I, Scholl S, Sayer H, Mügge LO, Hochhaus A, von Lilienfeld-Toal M Melphalan 200 mg/m 2 does not increase toxicity and improves survival in comparison to reduced doses of melphalan in multiple myeloma patients Bone Marrow Transplant. 2021;56(5):1209-1212

Brioli A, Manz K, Pfirrmann M, Hänel M, Schwarzer AC, Prange-Krex G, Fabisch C, Knop S, Illmer T, Krammer-Stein B, Hochhaus A, von Lilienfeld-Toal M, Mügge LO. Frailty impairs the feasibility of induction therapy but not of maintenance therapy in elderly myeloma patients: final results of the German Maintenance Study (GERMAIN) J Cancer Res Clin Oncol 2020;146(3):749-759

Kahl M, Brioli A, Bens M, Perner F, Kresinsky A, Schnetzke U, Hinze A, Sbirkov Y, Stengel S, Simonetti G, Martinelli G, Petrie K, Zelent A, Boehmer F, Groth M, Ernst T, Heidel F, Scholl S, Hochhaus A, Schenk T. The acetyltransferase GCN5 maintains ATRA-resistance in non-APL AML. Leukemia 2019;33(11)2628-2639

Walker BA, Boyle EM, Wardell CP, Murison A, Begum DB, Dahir NM, Proszek PZ, Johnson DC, Kaiser MF, Melchor L, Aronson LI, Scales M, Pawlyn C, Mirabella F, Jones JR, Brioli A, Mikulasova A, Cairns DA, Gregory WM, Quartilho A, Drayson MT, Russell N, Cook G, Jackson GH, Leleu X, Davies FE, Morgan GJ., Mutational Spectrum, Copy Number Changes, and Outcome: Results of a Sequencing Study of Patients With Newly Diagnosed Myeloma, J Clin Oncol. 2015;33(33):3911-20

Brioli A, Giles H, Pawlyn C, Campbell JP, Kaiser MF, Melchor L, Jackson GH, Gregory WM, Owen RG, Child JA, Davies FE, Cavo M, Drayson MT, Morgan GJ., Serum free immunoglobulin light chain evaluation as a marker of impact from intraclonal heterogeneity on myeloma outcome, Blood 2014; 123(22): 3414-9

Melchor L, Brioli A, Wardell CP, Murison A, Potter NE, Kaiser MF, Fryer RA, Johnson DC, Begum DB, Hulkki Wilson S, Vijayaraghavan G, Titley I, Cavo M, Davies FE, Walker BA, Morgan GJ, Single-cell genetic analysis reveals the composition of initiating clones and phylogenetic patterns of branching and parallel evolution in myeloma, Leukemia. 2014; 28(8): 1705-15.

Walker BA, Wardell CP, Melchor L, Brioli A, Johnson DC, Kaiser MF, Mirabella F, Lopez-Corral L, Humphray S, Murray L, Ross M, Bentley D, Gutiérrez NC, Garcia-Sanz R, San Miguel J, Davies FE, Gonzalez D, Morgan GJ, Intraclonal heterogeneity is a critical early event in the development of myeloma and precedes the development of clinical symptoms, Leukemia. 2014; 28(2): 384-90

Cavo M, Pantani L, Petrucci MT, Patriarca F, Zamagni E, Donnarumma D, Crippa C, Boccadoro M, Perrone G, Falcone A, Nozzoli C, Zambello R, Masini L, Furlan A, Brioli A, Derudas D, Ballanti S, Dessanti ML, De Stefano V, Carella AM, Marcatti M, Nozza A, Ferrara F, Callea V, Califano C, Pezzi A, Baraldi A, Grasso M, Musto P, Palumbo A., Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy following autologous hematopoietic stem-cell transplantation in patients with newly diagnosed multiple myeloma, Blood. 2012; 120(1): 9-19