Supplementary Materials

Supplementary Material for:

Dual inhibition of MDMX and MDM2 as a therapeutic strategy in leukemia

Luis A. Carvajal, Daniela Ben Neriah, Adrien Senecal, Lumie Benard, Victor Thiruthuvanathan, Tatyana Yatsenko, Swathi-Rao Narayanagari, Justin C. Wheat, Tihomira I. Todorova, Kelly Mitchell, Charles Kenworthy, Vincent Guerlavais, D. Allen Annis, Boris Bartholdy, Britta Will, Jesus D. Anampa, Ioannis Mantzaris, Manuel Aivado, Robert H. Singer, Robert A. Coleman, Amit Verma, Ulrich Steidl*

*Corresponding author. Email: ulrich.steidl{at}einstein.yu.edu

Published 11 April 2018, Sci. Transl. Med. 10, eaao3003 (2018)
DOI: 10.1126/scitranslmed.aao3003

This PDF file includes:

  • Materials and Methods
  • Fig. S1. MDMX is overexpressed in cancers of hematopoietic and lymphoid origin.
  • Fig. S2. MS2-SL repeats were inserted into a single allele of the p21 gene.
  • Fig. S3. ALRN-6924 disrupts the p53-MDM2 and p53-MDMX protein-protein interactions and activates p53-dependent pathways.
  • Fig. S4. MDMX-FL is differentially expressed in p53 WT AML cell lines sensitive to ALRN-6924.
  • Fig. S5. In vivo xenograft models of leukemia development are sensitive to ALRN-6924.
  • Fig. S6. Peripheral blood leukemic blasts from an MDS/AML patient treated with ALRN-6924 were analyzed by flow cytometry.
  • Table S1. ALRN-6924 binding kinetics to MDMX and MDM2 compared to RG7388, a small-molecule MDM2 inhibitor.
  • Table S2. Sensitivity of leukemia cell lines expressing WT and mutant p53 to ALRN-6924.
  • Legends for movies S1 and S2
  • References (8490)

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Other Supplementary Material for this manuscript includes the following:

  • Movie S1 (.avi format). Video showing transcriptional bursting of the p21 gene over time in vehicle-treated cells.
  • Movie S2 (.avi format). Video showing transcriptional bursting of the p21 gene over time in ALRN-6924–treated cells.

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