Immediate Effects of Dasatinib on the Migration and Redistribution of Naive and Memory Lymphocytes Associated With Lymphocytosis in Chronic Myeloid Leukemia Patients
Por:
Colom-Fernandez, B, Kreutzman, A, Marcos-Jimenez, A, Garcia-Gutierrez, V, Cuesta-Mateos, C, Portero-Sainz, I, Perez-Garcia, Y, Casado, LF, Sanchez-Guijo, F, Martinez-Lopez, J, Ayala, RM, Boque, C, Xicoy, B, Montero, I, Soto, C, Paz, R, Silva, G, Vega-Piris, L, Steegmann, JL and Munoz-Calleja, C
Publicada:
25 nov 2019
Ahead of Print:
25 nov 2019
Resumen:
Introduction: Dasatinib is a dual SRC/ABL tyrosine kinase inhibitor used to treat chronic myeloid leukemia (CML) that is known to have unique immunomodulatory effects. In particular, dasatinib intake typically causes lymphocytosis, which has been linked to better clinical response. Since the underlying mechanisms are unknown and SRC family kinases are involved in many cell motility processes, we hypothesized that the movement and migration of lymphocytes is modulated by dasatinib. Patients, Materials and Methods: Peripheral blood samples from CML patients treated with second-line dasatinib were collected before and 2 h after the first dasatinib intake, and follow-up samples from the same patients 3 and 6 months after the start of therapy. The migratory capacity and phenotype of lymphocytes and differential blood counts before and after drug intake were compared for all study time-points. Results: We report here for the first time that dasatinib intake is associated with inhibition of peripheral blood T-cell migration toward the homeostatic chemokines CCL19 and CCL21, which control the trafficking toward secondary lymphoid organs, mainly the lymph nodes. Accordingly, the proportion of lymphocytes in blood expressing CCR7, the chemokine receptor for both CCL19 and CCL21, decreased after the intake including both naive CD45RA+ and central memory CD45RO+ T-cells. Similarly, naive B-cells diminished with dasatinib. Finally, such changes in the migratory patterns did not occur in those patients whose lymphocyte counts remained unchanged after taking the drug. Discussion: We, therefore, conclude that lymphocytosis induced by dasatinib reflects a pronounced redistribution of naive and memory populations of all lymphocyte subsets including CD4+ and CD8+ T-cells and B-cells.
Filiaciones:
Colom-Fernandez, B:
UAM, Inst Invest Sanitaria Princesa IP, Hosp Univ La Princesa, Serv Immunol, Madrid, Spain
Kreutzman, A:
UAM, Inst Invest Sanitaria Princesa IP, Hosp Univ La Princesa, Serv Immunol, Madrid, Spain
Marcos-Jimenez, A:
UAM, Inst Invest Sanitaria Princesa IP, Hosp Univ La Princesa, Serv Immunol, Madrid, Spain
Garcia-Gutierrez, V:
Hosp Univ Ramon y Cajal, IRYCIS, Serv Hematol & Hemoterapia, Madrid, Spain
Cuesta-Mateos, C:
UAM, Inst Invest Sanitaria Princesa IP, Hosp Univ La Princesa, Serv Immunol, Madrid, Spain
Portero-Sainz, I:
UAM, Inst Invest Sanitaria Princesa IP, Hosp Univ La Princesa, Serv Immunol, Madrid, Spain
Perez-Garcia, Y:
UAM, Inst Invest Sanitaria Princesa IP, Hosp Univ La Princesa, Serv Immunol, Madrid, Spain
Casado, LF:
Hosp Virgen Salud, Serv Hematol & Hemoterapia, Toledo, Spain
Sanchez-Guijo, F:
IBSAL Hosp Univ Salamanca, Serv Hematol & Hemoterapia, Salamanca, Spain
Martinez-Lopez, J:
UCM, Hosp Univ 12 Octubre, Serv Hematol & Hernoterapia, CIBERONC, Madrid, Spain
Ayala, RM:
UCM, Hosp Univ 12 Octubre, Serv Hematol & Hernoterapia, CIBERONC, Madrid, Spain
Boque, C:
Inst Catala Oncol, Hosp Duran & Reynals, Serv Hematol Clin, Barcelona, Spain
:
Univ Autonoma Barcelona, Jose Carreras Leukemia Res Inst, Hosp Germans Trias & Pujol, Inst Catala Oncol,Serv Hematol Clin,Serv Hematol, Barcelona, Spain
Montero, I:
Hosp Univ Virgen del Rocio, Serv Hematol, Seville, Spain
Soto, C:
Hosp Povisa, Serv Hematol, Vigo, Spain
Paz, R:
Hosp Univ La Paz, Serv Hematol, Madrid, Spain
Silva, G:
Inst Invest Sanitaria Princesa IP, Hosp Univ La Princesa, Serv Hematol, Madrid, Spain
Vega-Piris, L:
Inst Invest Sanitaria Princesa IP, Unidad Metodol, Madrid, Spain
Steegmann, JL:
Inst Invest Sanitaria Princesa IP, Hosp Univ La Princesa, Serv Hematol, Madrid, Spain
Munoz-Calleja, C:
UAM, Inst Invest Sanitaria Princesa IP, Hosp Univ La Princesa, Serv Immunol, Madrid, Spain
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