Supplementary Materials

Supplementary Material for:

The caspase-8 inhibitor emricasan combines with the SMAC mimetic birinapant to induce necroptosis and treat acute myeloid leukemia

Gabriela Brumatti, Chunyan Ma, Najoua Lalaoui, Nhu-Y Nguyen, Mario Navarro, Maria C. Tanzer, Jennifer Richmond, Margherita Ghisi, Jessica M. Salmon, Natasha Silke, Giovanna Pomilio, Stefan P. Glaser, Elisha de Valle, Raffi Gugasyan, Mark A. Gurthridge, Stephen M. Condon, Ricky W. Johnstone, Richard Lock, Guy Salvesen, Andrew Wei, David L. Vaux, Paul G. Ekert,* John Silke*

*Corresponding author. Email: silke{at}wehi.edu.au (J.S.); paul.ekert{at}mcri.edu.au (P.G.E.)

Published 18 May 2016, Sci. Transl. Med. 8, 339ra69 (2016)
DOI: 10.1126/scitranslmed.aad3099

This PDF file includes:

  • Fig. S1. Endogenous protein expression in different AML subtypes.
  • Fig. S2. Generation of single-gene knockout leukemias.
  • Fig. S3. Generation of MLL-ENL birinapant-resistant cells.
  • Fig. S4. IDN-6556–mediated TNF-dependent necroptosis in different AML subtypes.
  • Fig. S5. Prevention of IDN-6556–induced cell death in human AML cells by inhibiting TNFR1 or RIPK1 kinase activity.
  • Fig. S6. Generation of MLL-ENL double-gene knockout leukemias.
  • Fig. S7. Biochemical comparison of caspase inhibitors IDN-6556, Z-VAD-FMK, and Q-VD-OPh.
  • Fig. S8. Comparison of the ability of caspase inhibitors to induce or block cell death in leukemic cells.
  • Fig. S9. Combined treatment with bir/IDN in vivo.
  • Fig. S10. Safety of combined bir/IDN treatment in healthy human cells.
  • Table S1. Deidentified patient data.

[Download PDF]