표제지
국문요약
목차
서론 10
재료 및 연구방법 12
결과 19
고찰 44
참고문헌 48
영문요약 54
Table 1. Information of cell lines 12
Table 2. Acute myeloid leukemia patient characteristics 14
Table 3. Information of antibodies 16
Table 4. Concentrations of FLT3-TKIs and YPN-005 for Bliss independence model score. 26
Table 5. Combination index (CI) values for combination of YPN-005 and FLT3 inhibitor in FLT3-ITD mutated acute myeloid leukemia cell lines. 28
Figure 1. Viability tests for combinations of YPN-005 and FLT3 inhibitors (Midostaurin, Quizaritinib, or Gilteritinib) compared to monotherapy in FLT3-ITD... 21
Figure 2. Inhibition of colony-forming ability of primary acute myeloid leukemia cells by YPN-005, FLT3 inhibitor (Quizartinib), or combination of both agents. The... 23
Figure 3. Synergistic effects of combination of YPN-005 and FLT3 inhibitors in FLT3-ITD mutated cell lines (MV4-11, MOLM-13, MOLM-14 and Ba/F3-ITD). (A-... 27
Figure 4. Cell cycle analysis of acute myeloid leukemia cell lines with FLT3-ITD following treatment with CDK7 inhibitor (YPN-005 [YPN]), FLT3 inhibitor (either... 31
Figure 5. Induction of apoptosis by the combined treatment of YPN-005 and FLT3 inhibitor against FLT3-ITD mutated acute myeloid leukemia cell lines. Apoptosis... 34
Figure 6. Induction of mitochondrial damage by combination with YPN-005 and FLT3 inhibitor. Change of mitochondrial membrane potential (MMP), △Ψm, in... 41
Figure 7. Antileukemic effects of YPN-005 combined with Quizartinib in in vivo acute myeloid leukemia models. YPN-005 of 1 mg/kg was intravenously... 43