CD49d promotes disease progression in chronic lymphocytic leukemia : new insights from CD49d bimodal expression
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Tissino, Erika
Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Italy
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Pozzo, Federico
Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Italy
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Benedetti, Dania
Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Italy
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Caldana, Chiara
Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Italy
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Bittolo, Tamara
Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Italy
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Rossi, Francesca Maria
Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Italy
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Bomben, Riccardo
Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Italy
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Nanni, Paola
Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Italy
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Chivilò, Hillarj
Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Italy
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Cattarossi, Ilaria
Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Italy
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Zaina, Eva
Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Italy
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Norris, Kevin
Division of Cancer and Genetics, School of Medicine, Cardiff University, United Kingdom
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Polesel, Jerry
Unit of Cancer Epidemiology, CRO, IRCCS, Aviano, Italy
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Gentile, Massimo
Hematology Unit, Azienda Ospedaliera (AO) of Cosenza, Italy
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Tripepi, Giovanni
Nephrology Center, National Research Institute of Biomedicine and Molecular Immunology, Reggio Calabria, Italy
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Moia, Riccardo
Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy
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Santinelli, Enrico
Division of Hematology, University of Tor Vergata, Rome, Italy
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Innocenti, Idanna
Dipartimento Scienze Radiologiche Radioterapiche ed Ematologiche, Fondazione Policlinico Universitario A Gemelli, IRCCS, Rome, Italy
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Olivieri, Jacopo
Clinica Ematologica, Centro Trapianti e Terapie Cellulari “Carlo Melzi” Dipartimento Interaziendale di Salute Mentale, AO Universitaria S. Maria Misericordia, Udine, Italy
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D’Arena, Giovanni
Onco-Haematology Department, Centro di Riferimento Oncologico della Basilicata, IRCCS, Rionero in Vulture, Italy
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Laurenti, Luca
Dipartimento Scienze Radiologiche Radioterapiche ed Ematologiche, Fondazione Policlinico Universitario A Gemelli, IRCCS, Rome, Italy
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Zaja, Francesco
Department of Internal Medicine and Hematology, Maggiore General Hospital, University of Trieste, Italy
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Pozzato, Gabriele
Department of Internal Medicine and Hematology, Maggiore General Hospital, University of Trieste, Italy
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Chiarenza, Annalisa
Division of Hematology, Ferrarotto Hospital, University of Catania, Italy
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Di Raimondo, Francesco
Division of Hematology, Ferrarotto Hospital, University of Catania, Italy
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Rossi, Davide
Hematology, Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland
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Pepper, Chris
Brighton and Sussex Medical School, University of Sussex, Brighton, United Kingdom
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Hartmann, Tanja Nicole
Department of Internal Medicine I, Medical Center and Faculty of Medicine, University of Freiburg, Germany
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Gaidano, Gianluca
Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy
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Del Poeta, Giovanni
Division of Hematology, University of Tor Vergata, Rome, Italy
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Gattei, Valter
Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Italy
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Zucchetto, Antonella
Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Italy
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Published in:
- Blood. - 2020, vol. 135, no. 15, p. 1244–1254
English
CD49d is a remarkable prognostic biomarker of chronic lymphocytic leukemia (CLL). The cutoff value for the extensively validated 30% of positive CLL cells is able to separate CLL patients into 2 subgroups with different prognoses, but it does not consider the pattern of CD49d expression. In the present study, we analyzed a cohort of 1630 CLL samples and identified the presence of ∼20% of CLL cases (n = 313) characterized by a bimodal expression of CD49d, that is, concomitant presence of a CD49d+ subpopulation and a CD49d− subpopulation. At variance with the highly stable CD49d expression observed in CLL patients with a homogeneous pattern of CD49d expression, CD49d bimodal CLL showed a higher level of variability in sequential samples, and an increase in the CD49d+ subpopulation over time after therapy. The CD49d+ subpopulation from CD49d bimodal CLL displayed higher levels of proliferation compared with the CD49d− cells; and was more highly represented in the bone marrow compared with peripheral blood (PB), and in PB CLL subsets expressing the CXCR4dim/CD5bright phenotype, known to be enriched in proliferative cells. From a clinical standpoint, CLL patients with CD49d bimodal expression, regardless of whether the CD49d+ subpopulation exceeded the 30% cutoff or not, experienced clinical behavior similar to CD49d+ CLL, both in chemoimmunotherapy (n = 1522) and in ibrutinib (n = 158) settings. Altogether, these results suggest that CD49d can drive disease progression in CLL, and that the pattern of CD49d expression should also be considered to improve the prognostic impact of this biomarker in CLL.
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https://n2t.net/ark:/12658/srd1319179
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