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 2020-01-31 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. application/pdf https://susi.usi.ch/global/documents/319179 https://n2t.net/ark:/12658/srd1319179 https://susi.usi.ch/documents/319179/files/Rossi_2020_blood_c_CD49d.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1182/blood.2019003179 info:eu-repo/semantics/altIdentifier/ark/12658/srd1319179 info:eu-repo/semantics/openAccess License undefined Blood. - 2020, vol. 135, no. 15, p. 1244–1254 Lymphoid neoplasia Chronic b-cell leukemias Chronic lymphocytic leukemia Disease progression Ibrutinib Prognostic marker Cxcr4 receptors Homogeneity info:eu-repo/classification/udc/61 CD49d promotes disease progression in chronic lymphocytic leukemia : new insights from CD49d bimodal expression http://purl.org/coar/resource_type/c_6501