CD49d promotes disease progression in chronic lymphocytic leukemia

Tissino, Erika; Pozzo, Federico; Benedetti, Dania; Caldana, Chiara; Bittolo, Tamara; Rossi, Francesca Maria; Bomben, Riccardo; Nanni, Paola; Chivilò, Hillarj; Cattarossi, Ilaria; Zaina, Eva; Norris, Kevin; Polesel, Jerry; Gentile, Massimo; Tripepi, Giovanni; Moia, Riccardo; Santinelli, Enrico; Innocenti, Idanna; Olivieri, Jacopo; D’Arena, Giovanni; Laurenti, Luca; Zaja, Francesco; Pozzato, Gabriele; Chiarenza, Annalisa; Di Raimondo, Francesco; Rossi, Davide; Pepper, Chris; Hartmann, Tanja Nicole; Gaidano, Gianluca; Del Poeta, Giovanni; Gattei, Valter; Zucchetto, Antonella

doi:10.1182/blood.2019003179

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Journal article

CD49d promotes disease progression in chronic lymphocytic leukemia : new insights from CD49d bimodal expression

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
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
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
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
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
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
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
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
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
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
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
Norris, Kevin Division of Cancer and Genetics, School of Medicine, Cardiff University, United Kingdom
Polesel, Jerry Unit of Cancer Epidemiology, CRO, IRCCS, Aviano, Italy
Gentile, Massimo Hematology Unit, Azienda Ospedaliera (AO) of Cosenza, Italy
Tripepi, Giovanni Nephrology Center, National Research Institute of Biomedicine and Molecular Immunology, Reggio Calabria, Italy
Moia, Riccardo Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy
Santinelli, Enrico Division of Hematology, University of Tor Vergata, Rome, Italy
Innocenti, Idanna Dipartimento Scienze Radiologiche Radioterapiche ed Ematologiche, Fondazione Policlinico Universitario A Gemelli, IRCCS, Rome, Italy
Olivieri, Jacopo Clinica Ematologica, Centro Trapianti e Terapie Cellulari “Carlo Melzi” Dipartimento Interaziendale di Salute Mentale, AO Universitaria S. Maria Misericordia, Udine, Italy
D’Arena, Giovanni Onco-Haematology Department, Centro di Riferimento Oncologico della Basilicata, IRCCS, Rionero in Vulture, Italy
Laurenti, Luca Dipartimento Scienze Radiologiche Radioterapiche ed Ematologiche, Fondazione Policlinico Universitario A Gemelli, IRCCS, Rome, Italy
Zaja, Francesco Department of Internal Medicine and Hematology, Maggiore General Hospital, University of Trieste, Italy
Pozzato, Gabriele Department of Internal Medicine and Hematology, Maggiore General Hospital, University of Trieste, Italy
Chiarenza, Annalisa Division of Hematology, Ferrarotto Hospital, University of Catania, Italy
Di Raimondo, Francesco Division of Hematology, Ferrarotto Hospital, University of Catania, Italy
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
Pepper, Chris Brighton and Sussex Medical School, University of Sussex, Brighton, United Kingdom
Hartmann, Tanja Nicole Department of Internal Medicine I, Medical Center and Faculty of Medicine, University of Freiburg, Germany
Gaidano, Gianluca Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy
Del Poeta, Giovanni Division of Hematology, University of Tor Vergata, Rome, Italy
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
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

31.01.2020

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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