Imatinib and plasmacytoid dendritic cell function in patients with chronic myeloid leukemia.
Plasmacytoid dendritic cells (PDCs) are crucial effectors in innate immunity. In this study, we show that imatinib, a potent inhibitor of BCR/ABL tyrosine kinase activity, in the presence of Flt3-Ligand, could induce CD34+ progenitors from chronic myeloid leukemia (CML) to give rise in vitro to typical BDCA-2+ type I interferon-producing PDCs. The effect of imatinib on PDC generation was related to up-regulation of Flt3 on leukemic CD34+ progenitors. Moreover, patients with chronic myeloid leukemia (CML) who were in complete cytogenetic or molecular response after imatinib treatment restored their blood PDCs both quantitatively and functionally comparable to healthy donors, in contrast to patients not responding to imatinib, further confirming that disease response to imatinib is accompanied by restoration of PDC function in vivo. These findings provide evidence that response to imatinib is capable to restore some DC-related immune functions in CML that might be beneficial for long-term disease control.
Mohty
Mohamad
M
Laboratoire d'Immunologie des Tumeurs, Institut Paoli-Calmettes, 232 Boulevard Sainte-Marguerite, 13273 Marseille Cedex 09, France.
Jourdan
Eric
E
Mami
Naira Ben
NB
Vey
Norbert
N
Damaj
Ghandi
G
Blaise
Didier
D
Isnardon
Daniel
D
Olive
Daniel
D
Gaugler
Béatrice
B
D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate