Gozzetti, A. (A.)
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- Molecular heterogeneity in AML/MDS patients with 3q21q26 rearrangements(Wiley-Blackwell, 2004) Gozzetti, A. (A.); Lahortiga, I. (Idoya); Vizmanos-Pérez, J.L. (José Luis); Vazquez, I. (Iria); Larrayoz, M.J. (María J.); Calasanz-Abinzano, M.J. (Maria Jose); Odero, M.D. (Maria Dolores); Aguirre-Ena, X. (Xabier)Patients with 3q21q26 rearrangements seem to share similar clinicopathologic features and a common molecular mechanism, leading to myelodysplasia or acute myeloid leukemia (AML). The ectopic expression of EVI1 (3q26) has been implicated in the dysplasia that characterizes this subset of myeloid neoplasias. However, lack of EVI1 expression has been reported in several cases, and overexpression of EVI1 was detected in 9% of AML cases without 3q26 abnormalities. We report the molecular characterization of seven patients with inv(3)(q21q26), t(3;3)(q21;q26) or related abnormalities. EVI1 expression was detected in only one case, and thus ectopic expression of this gene failed to explain all of these cases. GATA2 (3q21) was found to be overexpressed in 5 of the 7 patients. GATA2 is highly expressed in stem cells, and its expression dramatically decreases when erythroid and megakaryocytic differentiation proceeds. No mutations in GATA1 were found in any patient, excluding loss of function of GATA1 as the cause of GATA2 overexpression. We report finding molecular heterogeneity in patients with 3q21q26 rearrangements in both breakpoints and in the expression pattern of the genes near these breakpoints. Our data suggest that a unique mechanism is not likely to be involved in 3q21q26 rearrangements.
- 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.