Different immunoprofiles in patients with chronic myeloid leukemia treated with imatinib, nilotinib or dasatinib.
Immunomodulation induced by dasatinib is reportedly related to better prognosis in chronic myeloid leukemia (CML). However, the underlying mechanism has not yet been fully elucidated. The immunoprofiles of 63 patients in the chronic phase of CML were evaluated during treatment with a tyrosine kinase inhibitor (imatinib, n = 36; nilotinib, n = 9; dasatinib, n = 18). The numbers of CD56 + CD57 + and CD3 + CD57 + cells increased significantly in the dasatinib group. The numbers of regulatory T-cells were comparable among the three groups. Dasatinib markedly enhanced natural killer (NK)-cell reactivity. Only one patient treated with dasatinib showed a slight cytomegalovirus (CMV) reactivation. In contrast, nilotinib suppressed NK-cell reactivity. Plasma levels of interleukin-8 (IL-8), interferon-γ inducible protein-10 (IP-10) and monocyte chemoattractant protein-1 (MCP-1) were significantly elevated in all three groups, and plasma levels of granulocyte macrophage-colony stimulating factor (GM-CSF) were significantly elevated in the imatinib and dasatinib groups. Our results suggest the presence of a mechanism for dasatinib-associated immunomodulatory effects that is distinct from CMV reactivation and a decreased number of regulatory T-cells.
Graduate School of Medicine, Osaka City University, Osaka, Japan.
Yoshiki
Y
Hayashi
Hirohisa
H
Nakamae
Takako
T
Katayama
Takahiko
T
Nakane
Hideo
H
Koh
Mika
M
Nakamae
Asao
A
Hirose
Kiyoyuki
K
Hagihara
Yoshiki
Y
Terada
Yoshitaka
Y
Nakao
Masayuki
M
Hino
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D018925:Chemokines / Q000097:blood / Q000378:metabolism; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D000069439:Dasatinib; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D016130:Immunophenotyping; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use*; D013844:Thiazoles / Q000627:therapeutic use*; D055815:Young Adult
D000970:Antineoplastic Agents; D001549:Benzamides; D018925:Chemokines; D016207:Cytokines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; C498826:nilotinib; D000069439:Dasatinib