Page 8 - D. Cancer biology

[D. Cancer biology-4]

FLT3-TAZ Signaling in Hematologic Malignancy

Ji Eun Shin¹, Hyun Woo Park¹

¹Biochemistry, Yonsei University, Seoul 03722, Republic of Korea

YAP/TAZ, the transcriptional co-activators of TEAD and major transducers of the Hippo pathway, has been studied
only in solid tumors. Interestingly, YAP/TAZ are consistently upregulated in adherent tumor cell lines but hardly
expressed in hematologic malignancies including lymphoma and leukemia. Hence, the role of YAP/TAZ in leukemia

has not been explored. Many FLT3 studies have been focused on acute myeloid leukemia, while few reports have

been published in chronic myeloid leukemia. However, we identified significant upregulation of TAZ in blast crisis
phase CML. We observed a strong correlation between TAZ and FLT3 induction in bc-CML patients as well as
leukemia cells, which led us to investigate the role of FLT3-TAZ signaling in bc-CML. FLT3, TAZ expression induced

Imatinib, Nilotinib, Dasatinib resistance in K562 cells line. Our data show that CD36, the target gene of TAZ/TEAD,
are upregulated promotes TKI resistance. We found out that FLT3-JAK-STAT3-TAZ-TEAD-CD36 axis confers drug

resistance in bc-CML. Importantly, inhibition each of FLT3, TAZ, TEAD, CD36 re-sensitized K562-FLT3-IR cell to TKI
treatment and caused cell death. Therefore, we purpose that combination therapy targeting both FLT3-TAZ and

Bcr/Abl signaling triggers synthetic lethality in bc-CML.