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Flow cytometry for fast screening and automated risk assessment in systemic light-chain amyloidosis

AuthorsPuig, Noemi; Paiva, Bruno; Lasa, Marta; Burgos, Leire; Pérez, José J.; Merino, Juana; Moreno, Cristina; Vidriales, Maria Belén; Gómez Toboso, Dolores; Cedena, Maria-Teresa; Ocio, Enrique M. ; Lécumberri, Ramon; García de Coca, Alfonso; Labrador, Jorge; Gonzalez, Maria-Esther; Palomera, Luis; Gironella, Mercedes; Cabañas, Valentin; Casanova, María; Oriol, Albert; Krsnik, Isabel; Pérez-Montaña, Albert; Rubia, Javier de la; Puerta, Jose-Enrique de la; Arriba, Felipe de; Prosper, Felipe; Martínez-López, Joaquín; Lécrevisse, Quentin; Verde, Javier; Mateos, Maria Victoria; Lahuerta, Juan José; Orfao, Alberto ; San Miguel, Jesús F.
KeywordsHaematological cancer
Translational research
Issue Date2019
PublisherSpringer Nature
CitationLeukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 33: 1256-1267 (2019)
AbstractEarly diagnosis and risk stratification are key to improve outcomes in light-chain (AL) amyloidosis. Here we used multidimensional-flow-cytometry (MFC) to characterize bone marrow (BM) plasma cells (PCs) from a series of 166 patients including newly-diagnosed AL amyloidosis (N = 94), MGUS (N = 20) and multiple myeloma (MM, N = 52) vs. healthy adults (N = 30). MFC detected clonality in virtually all AL amyloidosis (99%) patients. Furthermore, we developed an automated risk-stratification system based on BMPCs features, with independent prognostic impact on progression-free and overall survival of AL amyloidosis patients (hazard ratio: ≥ 2.9;P ≤.03). Simultaneous assessment of the clonal PCs immunophenotypic protein expression profile and the BM cellular composition, mapped AL amyloidosis in the crossroad between MGUS and MM; however, lack of homogenously-positive CD56 expression, reduction of B-cell precursors and a predominantly-clonal PC compartment in the absence of an MM-like tumor PC expansion, emerged as hallmarks of AL amyloidosis (ROC-AUC = 0.74;P <.001), and might potentially be used as biomarkers for the identification of MGUS and MM patients, who are candidates for monitoring pre-symptomatic organ damage related to AL amyloidosis. Altogether, this study addressed the need for consensus on how to use flow cytometry in AL amyloidosis, and proposes a standardized MFC-based automated risk classification ready for implementation in clinical practice.
Publisher version (URL)http://dx.doi.org/10.1038/s41375-018-0308-5
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