TY - JOUR
T1 - Role of the STAT1 pathway in apoptosis induced by fludarabine and JAK kinase inhibitors in B-cell chronic lymphocytic leukemia
AU - Martinez-Lostao, Luis
AU - Briones, Javier
AU - Forné, Ignasi
AU - Martinez-Gallo, Monica
AU - Ferrer, Beatriz
AU - Sierra, Jordi
AU - Rodriguez-Sanchez, Jose Luis
AU - Juarez, Candido
N1 - Funding Information:
This work was supported by grants from the Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo (FIS 00/0605) and Comissionat per a Universitats i Recerca (III Pla de Recerca de Catalunya, Exp. 2001SGR 00397). We thank Carolyn Newey and Ignasi Gich for their help with the preparation of the manuscript. We are also grateful to members of the Departments of Immunology and Hematology for their support.
PY - 2005/3
Y1 - 2005/3
N2 - Signal transducers and activators of transcription (STAT) proteins comprise a family of transcription factors that have been implicated in tumoral transformation, especially in hematological malignancies. Because of this, the JAK/STAT pathway is attractive as a therapeutic target in these tumors. In the present study, we analyzed the ability of fludarabine and two JAK kinase inhibitors, AG490 and WHI-P131, to block STAT1 activation and induce apoptosis on B-cell chronic lymphocytic leukemia (B-CLL) cells. All drugs were able to induce a high percentage of apoptosis on B-CLL cells from all patients studied. However, only AG490 and WHI-P131 were able to strongly suppress the STAT1 activation of B-CLL cells. In conclusion, our data show that JAK kinase inhibitors, such as AG490 and WHI-P131 are able to inhibit the STAT1 pathway on B-CLL cells and are strong inductors of apoptosis on these cells.
AB - Signal transducers and activators of transcription (STAT) proteins comprise a family of transcription factors that have been implicated in tumoral transformation, especially in hematological malignancies. Because of this, the JAK/STAT pathway is attractive as a therapeutic target in these tumors. In the present study, we analyzed the ability of fludarabine and two JAK kinase inhibitors, AG490 and WHI-P131, to block STAT1 activation and induce apoptosis on B-cell chronic lymphocytic leukemia (B-CLL) cells. All drugs were able to induce a high percentage of apoptosis on B-CLL cells from all patients studied. However, only AG490 and WHI-P131 were able to strongly suppress the STAT1 activation of B-CLL cells. In conclusion, our data show that JAK kinase inhibitors, such as AG490 and WHI-P131 are able to inhibit the STAT1 pathway on B-CLL cells and are strong inductors of apoptosis on these cells.
KW - AG490
KW - Apoptosis
KW - B-CLL
KW - Fludarabine
KW - STAT1
KW - WHI-P131
UR - http://www.scopus.com/inward/record.url?scp=13544249962&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=13544249962&partnerID=8YFLogxK
U2 - 10.1080/10428190400018398
DO - 10.1080/10428190400018398
M3 - Article
C2 - 15621835
AN - SCOPUS:13544249962
SN - 1042-8194
VL - 46
SP - 435
EP - 442
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 3
ER -
