Abstract
| Original language | English |
|---|---|
| Article number | 1787 |
| Journal | Nature Communications |
| Volume | 9 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2018 |
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A retinoic acid-dependent stroma-leukemia crosstalk promotes chronic lymphocytic leukemia progression. / Farinello, D; Wozińska, M; Lenti, E; Genovese, L; Bianchessi, S; Migliori, E; Sacchetti, N; Di Lillo, A; Bertilaccio, MTS; De Lalla, C; Valsecchi, R; Gleave, SB; Lligé, D; Scielzo, C; Mauri, Laura; Ciampa, MG; Scarfò, L; Bernardi, R; Lazarevic, D; Gonzalez-Farre, B; Bongiovanni, L; Campo, E; Cerutti, A; Ponzoni, M; Pattini, L; Caligaris-Cappio, F; Ghia, P; Brendolan, A.
In: Nature Communications, Vol. 9, No. 4, 1787, 2018.Research output: Contribution to journal › Article
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TY - JOUR
T1 - A retinoic acid-dependent stroma-leukemia crosstalk promotes chronic lymphocytic leukemia progression
AU - Farinello, D
AU - Wozińska, M
AU - Lenti, E
AU - Genovese, L
AU - Bianchessi, S
AU - Migliori, E
AU - Sacchetti, N
AU - Di Lillo, A
AU - Bertilaccio, MTS
AU - De Lalla, C
AU - Valsecchi, R
AU - Gleave, SB
AU - Lligé, D
AU - Scielzo, C
AU - Mauri, Laura
AU - Ciampa, MG
AU - Scarfò, L
AU - Bernardi, R
AU - Lazarevic, D
AU - Gonzalez-Farre, B
AU - Bongiovanni, L
AU - Campo, E
AU - Cerutti, A
AU - Ponzoni, M
AU - Pattini, L
AU - Caligaris-Cappio, F
AU - Ghia, P
AU - Brendolan, A
PY - 2018
Y1 - 2018
N2 - In chronic lymphocytic leukemia (CLL), the non-hematopoietic stromal microenvironment plays a critical role in promoting tumor cell recruitment, activation, survival, and expansion. However, the nature of the stromal cells and molecular pathways involved remain largely unknown. Here, we demonstrate that leukemic B lymphocytes induce the activation of retinoid acid synthesis and signaling in the microenvironment. Inhibition of RA-signaling in stromal cells causes deregulation of genes associated with adhesion, tissue organization and chemokine secretion including the B-cell chemokine CXCL13. Notably, reducing retinoic acid precursors from the diet or inhibiting RA-signaling through retinoid-antagonist therapy prolong survival by preventing dissemination of leukemia cells into lymphoid tissues. Furthermore, mouse and human leukemia cells could be distinguished from normal B-cells by their increased expression of Rarγ2 and RXRα, respectively. These findings establish a role for retinoids in murine CLL pathogenesis, and provide new therapeutic strategies to target the microenvironment and to control disease progression. © 2018 The Author(s).
AB - In chronic lymphocytic leukemia (CLL), the non-hematopoietic stromal microenvironment plays a critical role in promoting tumor cell recruitment, activation, survival, and expansion. However, the nature of the stromal cells and molecular pathways involved remain largely unknown. Here, we demonstrate that leukemic B lymphocytes induce the activation of retinoid acid synthesis and signaling in the microenvironment. Inhibition of RA-signaling in stromal cells causes deregulation of genes associated with adhesion, tissue organization and chemokine secretion including the B-cell chemokine CXCL13. Notably, reducing retinoic acid precursors from the diet or inhibiting RA-signaling through retinoid-antagonist therapy prolong survival by preventing dissemination of leukemia cells into lymphoid tissues. Furthermore, mouse and human leukemia cells could be distinguished from normal B-cells by their increased expression of Rarγ2 and RXRα, respectively. These findings establish a role for retinoids in murine CLL pathogenesis, and provide new therapeutic strategies to target the microenvironment and to control disease progression. © 2018 The Author(s).
U2 - 10.1038/s41467-018-04150-7
DO - 10.1038/s41467-018-04150-7
M3 - Article
VL - 9
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 4
M1 - 1787
ER -