Geraldes, C. (Catarina)
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- Preneoplastic somatic mutations including MYD88(L265P) in lymphoplasmacytic lymphoma(2022) Reinhardt, H.C. (Hans Christian); Vilas, A. (Amaia); Sanchez-Garcia, I. (Isidro); Perez, C. (Cristina); Paiva, A. (Artur); López-de-Arancibia, A. (Aitziber); Sacco, A. (Antonio); Santos, S. (S.); Celay, J. (Jon); Sarvide, S. (Sarai); García-Sanz, R. (Ramón); Goicoechea, I. (Ibai); García-Barchino, M.J. (María José); Martinez-Climent, J.A. (José Ángel); Gárate-Luzuriaga, S. (Sonia); Carrasco, Y.R. (Yolanda R.); Panizo, C. (Carlos); Larrayoz, M. (Marta); Vitoria, H. (Helena); Puig, N. (Noemí); Botta, C. (Cirino); Rodríguez-Díaz, S. (Saray); Garcés-Latre, J.J. (Juan José); Motta, M. (Marina); Geraldes, C. (Catarina); Lamo-de-Espinosa-Vázquez-de-Sola, J.M. (José María); Alignani, D. (Diego); Duarte, S. (Sara); Paiva, B. (Bruno); Larrayoz, M.J. (María J.); Prosper-Cardoso, F. (Felipe); Calasanz-Abinzano, M.J. (Maria Jose); Roccaro, A.M. (Aldo M.); Fuerte, G. (Gema); Tucci, A. (Alessandra); San-Miguel, J.F. (Jesús F.); Gentile, M. (Massimo); Jiménez, C. (Cristina)Normal cell counterparts of solid and myeloid tumors accumulate mutations years before disease onset; whether this occurs in B lymphocytes before lymphoma remains uncertain. We sequenced multiple stages of the B lineage in elderly individuals and patients with lymphoplasmacytic lymphoma, a singular disease for studying lymphomagenesis because of the high prevalence of mutated MYD88. We observed similar accumulation of random mutations in B lineages from both cohorts and unexpectedly found MYD88(L265P) in normal precursor and mature B lymphocytes from patients with lymphoma. We uncovered genetic and transcriptional pathways driving malignant transformation and leveraged these to model lymphoplasmacytic lymphoma in mice, based on mutated MYD88 in B cell precursors and BCL2 overexpression. Thus, MYD88(L265P) is a preneoplastic event, which challenges the current understanding of lymphomagenesis and may have implications for early detection of B cell lymphomas.
- Insights on multiple myeloma treatment strategies(Ovid Technologies (Wolters Kluwer Health), 2018) Moreau, P. (Philippe); Hansson, M. (Markus); Boccadoro, M. (Mario); Delforge, M. (M.); Straka, C. (Christian); Bladé, J. (Joan); Masszi, T. (Tamás); Cavo, M. (Michele); Ludwig, H. (Heinz); Hajek, R. (R.); Mateos, M.V. (María Victoria); Zver, S. (Samo); Jamroziak, K. (Krzysztof); Sonneveld, P. (Pieter); Beksac, M. (Meral); O’Dwyer, M. (Michael); Bazarbachi, A. (Ali); Yong, K. (Kwee); Donk, N.W.C.J. (Niels W.C.J.) van de; Geraldes, C. (Catarina); Facon, T. (Thierry); Goldschmidt, H. (Hartmut); Dimopoulos, M.A. (Meletios A.); Mendeleeva, L. (Larisa); Plesner, T. (Torben); Leiba, M. (Merav); San-Miguel, J.F. (Jesús F.)The introduction of new agents and management strategies over the past decade has resulted in a major step change in treatment outcomes with deepening responses and increased survival for patients with multiple myeloma. In daily clinical practice, healthcare professionals are now faced with challenges including, optimal treatment sequencing and changing treatment goals. In light of this, a group of experts met to discuss diagnostic and treatment guidelines, examine current clinical practice, and consider how new clinical trial data may be integrated into the management of multiple myeloma in the future.
- International Myeloma Working Group risk stratification model for smoldering multiple myeloma (SMM)(2020) Gonzalez-Calle, V. (Veronica); Durie, B. (B.); Hansson, M. (Markus); Ukropec, J. (Jon); Usmani, S.Z. (Saad Z.); Merlini, G. (G.); Zamagni, E. (Elena); Min, C.K. (Chang-Ki); Qi, M. (Ming); Ludwig, H. (Heinz); Hajek, R. (R.); Mateos, M.V. (María Victoria); De-Larrea, C.F. (Carlos Fernández); Esteves, G. (Graça); Kumar, S. (Shaji); Gozzetti, A. (A.); Morgan, G.J. (Gareth J.); Geraldes, C. (Catarina); Kyriakou, C. (Charalampia); Goldschmidt, H. (Hartmut); Kim, B.S. (Byung-Su); Dimopoulos, M.A. (Meletios A.); Kastritis, E. (Efstathios); Weiss, B.M. (Brendan M.); Fantl, D. (Dorotea); Rajkumar, S.V. (S. Vincent); San-Miguel, J.F. (Jesús F.); Leleu, X. (Xavier); Garderet, L. (Laurent)Smoldering multiple myeloma (SMM) is an asymptomatic precursor state of multiple myeloma (MM). Recently, MM was redefined to include biomarkers predicting a high risk of progression from SMM, thus necessitating a redefinition of SMM and its risk stratification. We assembled a large cohort of SMM patients meeting the revised IMWG criteria to develop a new risk stratification system. We included 1996 patients, and using stepwise selection and multivariable analysis, we identified three independent factors predicting progression risk at 2 years: serum M-protein >2 g/dL (HR: 2.1), involved to uninvolved free light-chain ratio >20 (HR: 2.7), and marrow plasma cell infiltration >20% (HR: 2.4). This translates into 3 categories with increasing 2-year progression risk: 6% for low risk (38%; no risk factors, HR: 1); 18% for intermediate risk (33%; 1 factor; HR: 3.0), and 44% for high risk (29%; 2–3 factors). Addition of cytogenetic abnormalities (t(4;14), t(14;16), +1q, and/or del13q) allowed separation into 4 groups (low risk with 0, low intermediate risk with 1, intermediate risk with 2, and high risk with ≥3 risk factors) with 6, 23, 46, and 63% risk of progression in 2 years, respectively. The 2/20/20 risk stratification model can be easily implemented to identify high-risk SMM for clinical research and routine practice and will be widely applicable.