Supplementary Materials

Supplementary Material for:

A therapeutically targetable mechanism of BCR-ABL–independent imatinib resistance in chronic myeloid leukemia

Leyuan Ma, Yi Shan, Robert Bai, Liting Xue, Christopher A. Eide, Jianhong Ou, Lihua J. Zhu, Lloyd Hutchinson, Jan Cerny, Hanna Jean Khoury, Zhi Sheng, Brian J. Druker, Shaoguang Li, Michael R. Green*

*Corresponding author. E-mail: michael.green@umassmed.edu

Published 3 September 2014, Sci. Transl. Med. 6, 252ra121 (2014)
DOI: 10.1126/scitranslmed.3009073

This PDF file includes:

  • Materials and Methods
  • Fig. S1. IM sensitivity of nonvalidating candidates isolated from the primary shRNA screen.
  • Fig. S2. Confirmation of validating candidates with a second shRNA.
  • Fig. S3. IM sensitivity after candidate IMSG KD in mouse primary bone marrow cells.
  • Fig. S4. Relative IC50 IM of candidate IMSG KD K562 cells.
  • Fig. S5. Increased PRKCH and PKCη after IMSG KD in K562 cells.
  • Fig. S6. Direct transcriptional repression of PRKCH by ELF5.
  • Fig. S7. Confirmation of increased PKCη in K562/PRKCH cells and role of PRKCH in IM resistance.
  • Fig. S8. Confirmation that PKCη functions through CRAF to increase RAF/MEK/ERK signaling.
  • Fig. S9. Comparison of combined treatment with IM and trametinib to IM and a JAK-STAT or PI3K inhibitor.
  • Fig. S10. Effectiveness of retroviruses coexpressing BCR-ABL and either PRKCH or an Elf5 or Clec5a shRNA.
  • Fig. S11. Decreased colony formation after KD of PRKCH in BCR-ABL+ cells.
  • Fig. S12. Confirmation of IM sensitivity of murine CML progenitor cells.
  • Fig. S13. Quantification of phosphorylated ERK1/2 in CML progenitor and stem cells.
  • Fig. S14. Synergistic induction of apoptosis in murine CML stem cells by IM and trametinib.
  • Fig. S15. Effect of IM and trametinib on normal hematopoietic stem cells.
  • Table S1. List of 11 IMSGs obtained from the genome-wide RNAi screen.
  • Legend for table S2
  • Table S3. Relative expression of IMSGs in IM-resistant BCR-ABL wild-type CML patient samples.
  • Legends for tables S4 and S5
  • Table S6. List of clone IDs for shRNAs obtained from Open Biosystems/Thermo Scientific.
  • Table S7. List of primer sequences used for qRT-PCR.
  • References (6569)

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Other Supplementary Material for this manuscript includes the following:

  • Table S2. List of CML patient samples used in this study (provided as a separate Excel file).
  • Table S4. Actual P values for all comparisons in this study (provided as a separate Excel file).
  • Table S5. Original data for composite figures from experiments with mice and primary human samples (provided as a separate Excel file).

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