INBIRS   24491
INSTITUTO DE INVESTIGACIONES BIOMEDICAS EN RETROVIRUS Y SIDA
Unidad Ejecutora - UE
artículos
Título:
The Expression of Sphingosine-1 Phosphate Receptor-1 in
Autor/es:
BORGE M; REMES LENICOV F; NANNINI PR; DE LOS RÍOS ALICANDÚ MM; PODAZA E,; CEBALLOS A; GIORDANO; GAMBERALE R
Revista:
JOURNAL OF IMMUNOLOGY
Editorial:
AMER ASSOC IMMUNOLOGISTS
Referencias:
Lugar: Bethesda; Año: 2014 p. 193 - 196
ISSN:
0022-1767
Resumen:
Chronic lymphocytic leukemia (CLL) is characterized by the progressive accumulation of clonal B lymphocytes. Proliferation
occurs in lymphoid tissues upon interaction of leukemic cells with a supportive microenvironment. Therefore, the mobilization of
tissue-resident CLL cells into the circulation is a useful therapeutic strategy to minimize the reservoir of tumor cells within
survival niches. Because the exit of normal lymphocytes from lymphoid tissues depends on the presence of sphingosine-1 phosphate
(S1P) and the regulated expression of S1P receptor-1 (S1PR1), we investigated whether the expression and function of
S1PR1 can be modulated by key microenvironment signals. We found that activation of CLL cells with CXCL12, fibroblast
CD40L+, BCR cross-linking, or autologous nurse-like cells reduces their S1PR1 expression and the migratory response toward
S1P. Moreover, we found that S1PR1 expression was reduced in the proliferative/activated subset of leukemic cells compared with
the quiescent subset from the same patient. Similarly, bone marrow?resident CLL cells expressing high levels of the activation
marker CD38 showed a lower expression of S1PR1 compared with CD38low counterparts. Finally, given that treatment with BCRassociated
kinase inhibitors induces a transient redistribution of leukemic cells from lymphoid tissues to circulation, we studied
the effect of the Syk inhibitors piceatannol and R406 on S1PR1 expression and function. We found that they enhance S1PR1 expression
in CLL cells and their migratory response toward S1P. Based on our results, we suggest that the regulated expression of S1PR1
might modulate the egress of the leukemic clone from lymphoid tissues.
kinase inhibitors induces a transient redistribution of leukemic cells from lymphoid tissues to circulation, we studied
the effect of the Syk inhibitors piceatannol and R406 on S1PR1 expression and function. We found that they enhance S1PR1 expression
in CLL cells and their migratory response toward S1P. Based on our results, we suggest that the regulated expression of S1PR1
might modulate the egress of the leukemic clone from lymphoid tissues.
S1P. Moreover, we found that S1PR1 expression was reduced in the proliferative/activated subset of leukemic cells compared with
the quiescent subset from the same patient. Similarly, bone marrow?resident CLL cells expressing high levels of the activation
marker CD38 showed a lower expression of S1PR1 compared with CD38low counterparts. Finally, given that treatment with BCRassociated
kinase inhibitors induces a transient redistribution of leukemic cells from lymphoid tissues to circulation, we studied
the effect of the Syk inhibitors piceatannol and R406 on S1PR1 expression and function. We found that they enhance S1PR1 expression
in CLL cells and their migratory response toward S1P. Based on our results, we suggest that the regulated expression of S1PR1
might modulate the egress of the leukemic clone from lymphoid tissues.
kinase inhibitors induces a transient redistribution of leukemic cells from lymphoid tissues to circulation, we studied
the effect of the Syk inhibitors piceatannol and R406 on S1PR1 expression and function. We found that they enhance S1PR1 expression
in CLL cells and their migratory response toward S1P. Based on our results, we suggest that the regulated expression of S1PR1
might modulate the egress of the leukemic clone from lymphoid tissues.
+, BCR cross-linking, or autologous nurse-like cells reduces their S1PR1 expression and the migratory response toward
S1P. Moreover, we found that S1PR1 expression was reduced in the proliferative/activated subset of leukemic cells compared with
the quiescent subset from the same patient. Similarly, bone marrow?resident CLL cells expressing high levels of the activation
marker CD38 showed a lower expression of S1PR1 compared with CD38low counterparts. Finally, given that treatment with BCRassociated
kinase inhibitors induces a transient redistribution of leukemic cells from lymphoid tissues to circulation, we studied
the effect of the Syk inhibitors piceatannol and R406 on S1PR1 expression and function. We found that they enhance S1PR1 expression
in CLL cells and their migratory response toward S1P. Based on our results, we suggest that the regulated expression of S1PR1
might modulate the egress of the leukemic clone from lymphoid tissues.
kinase inhibitors induces a transient redistribution of leukemic cells from lymphoid tissues to circulation, we studied
the effect of the Syk inhibitors piceatannol and R406 on S1PR1 expression and function. We found that they enhance S1PR1 expression
in CLL cells and their migratory response toward S1P. Based on our results, we suggest that the regulated expression of S1PR1
might modulate the egress of the leukemic clone from lymphoid tissues.
low counterparts. Finally, given that treatment with BCRassociated
kinase inhibitors induces a transient redistribution of leukemic cells from lymphoid tissues to circulation, we studied
the effect of the Syk inhibitors piceatannol and R406 on S1PR1 expression and function. We found that they enhance S1PR1 expression
in CLL cells and their migratory response toward S1P. Based on our results, we suggest that the regulated expression of S1PR1
might modulate the egress of the leukemic clone from lymphoid tissues.