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CD49d promotes disease progression in chronic lymphocytic leukemia: new insights from CD49d bimodal expression
journal contribution
posted on 2023-06-09, 20:42 authored by Erika Tissino, Federico Pozzo, Dania Benedetti, Chiara Caldana, Tamara Bittolo, Francesca Maria Rossi, Riccardo Bomben, Paola Nanni, Hillarj Chivilò, Ilaria Cattarossi, Eva Zaina, Kevin Norris, Jerry Polesel, Massimo Gentile, Christopher PepperChristopher Pepper, othersCD49d is a remarkable prognostic biomarker of chronic lymphocytic leukemia (CLL). The extensively validated 30% of positive CLL cells cut-off value is able to separate CLL patients into two subgroups with different prognosis, but it does not consider the pattern of CD49d expression. In the present study, we analysed a cohort of 1,630 CLL samples and identified the presence of ~20% of CLL cases (n=313) characterized by a bimodal expression of CD49d, i.e. concomitant presence of a CD49dpos sub-population and a CD49dneg sub-population. 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 CD49dpos sub-population over time after therapy. The CD49dpos sub-population from CD49d bimodal CLL displayed higher levels of proliferation compared to the CD49dneg cells, was more highly represented in the bone marrow compared to 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 CD49dpos sub-population exceeded or not the 30% cut-off, experienced a clinical behavior similar to CD49dpos CLL, both in the chemo-immunotherapy (n=1,522) and in the ibrutinib (n=158) settings. Altogether, these results suggest that CD49d can drive disease progression in CLL, and that the pattern of CD49d expression should be also considered to improve the prognostic impact of this biomarker in CLL.
History
Publication status
- Published
File Version
- Accepted version
Journal
BloodISSN
0006-4971Publisher
American Society of HematologyExternal DOI
Issue
15Volume
135Page range
1244-1254Department affiliated with
- Clinical and Experimental Medicine Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2020-02-25First Open Access (FOA) Date
2021-02-01First Compliant Deposit (FCD) Date
2020-02-27Usage metrics
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