作者: Lucas Gutierrez , Miran Jang , Tian Zhang , Mojtaba Akhtari , Houda Alachkar
DOI: 10.1038/S41598-018-35978-0
关键词: Myeloid 、 Leukemia 、 Midostaurin 、 T cell 、 Cancer research 、 Stem cell 、 Myeloid leukemia 、 Medicine 、 Population 、 FOXP3
摘要: Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy in which the only curative approach allogeneic stem cell transplant (Allo-HSCT). The recognition and elimination of leukemic clones by donor T-cells contribute significantly to Allo-HSCT success. FLT3-ITD, common mutation AML, associated with poor prognosis. Recently, midostaurin became first FDA approved FLT3-inhibitor for pre-transplant patients FLT3-ITD combination standard therapy. In addition their multikinase activity may affect T-cell signaling, FLT3-inhibitors induce apoptosis malignant cells also enhance antigen presentation activate T-cells. Considering increased clinical use these inhibitors limited benefit derived from as single agents, understanding how T population function needed improve benefit. We examined effect four different FLT3 (midostaurin, sorafenib, tandutinib, quizartenib) on populations peripheral blood mononuclear (PBMC) obtained healthy donors AML. Midostaurin exhibited significant decrease CD4 + CD25 + FOXP3+ FOXP3 mRNA expression AML PBMCs. Similarly, samples collected treated showed reduction Tregs markers. Interferon-γ(IFN-γ), tumor necrosis factor-α(TNF-α), IL-10 levels were reduced following treatment. approval setting, our finding will have important implication it provides rationale functional investigation post-transplant patients.