Supplementary Materials

The PDF file includes:

  • Materials and methods
  • Fig. S1. Isolation and characterization of human primary hematopoietic cells from umbilical cord blood.
  • Fig. S2. Proportion of differentiated cells, dying or dead cells, and self-renewing cells in populations of cord blood cells transduced with MLL-ENL or MLL-AF6.
  • Fig. S3. Bioinformatic analysis of differentially expressed genes in MLLx-transduced populations of cord blood cells.
  • Fig. S4. Characteristics of primary leukemias induced by transplantation of HSC-derived or CMP-derived MLLx-transformed cells.
  • Fig. S5. HSC-derived and CMP-derived MLL-AML cells contain CSCs that induce leukemia in secondary recipient mice.
  • Fig. S6. LTC-IC activity is highest in the CD34−/lo/CD38+ subpopulation of AML cells from patients.
  • Fig. S7. CD34CD38+ subpopulation of human AML cells engrafts after transplantation into NSG mice.
  • Fig. S8. Fully functional CSCs reside in the CD34/loCD38+ subpopulation.
  • Fig. S9. HSC-like genetic signature is associated with poor prognosis of patients with AML.
  • Fig. S10. HSC-derived or HSC-like MLLx AML cells are resistant to chemotherapy.
  • Fig. S11. Knocking down or inhibition of ABCC3 sensitizes HSC-MLLx cells to DOXO.
  • Fig. S12. Fidaxomicin and DOXO combination therapy is effective against HSC-like human MLL-AML in a xenograft model.
  • Fig. S13. Schematic diagram of the human origins and underlying mechanisms of treatment resistance in MLL-AML stem cells.
  • Table S1. Immunotype of primary MLL-fusion cell lines, cells from the recipient animals and primary patient samples.
  • Table S2. List of samples used for bioinformatic analysis.
  • Table S3. Differential gene analysis by DeSeq2 and one-way ANOVA test after rlog and vst transformation.
  • Table S4. List of genes differentially up-regulated in HSC/CMP (45 genes) and LMPP/GMP (130 genes).
  • Table S5. Functional annotation by Toppgene and Webgestalt (2013 version).
  • Table S6. Acquired SNVs in leukemic samples.
  • Table S7. In vivo limiting dilution analysis of cord blood-derived MLL-AF6; cell dose and response.
  • Table S8. Patient clinical particular.
  • Table S9. In vivo limiting dilution analysis of primary patient samples; cell dose and response.
  • Table S10. Signal genes used in neural network.
  • Table S11. Neural network training and test sets.
  • Table S12. Neural network classification for patients in microarray sets.
  • Table S13. Multivariate analysis of variables affecting overall survival.
  • Table S14. Neural network classification for MLL-fusion patients.
  • Table S15. Ninety-nine genes differentially expressed in transformed HSC-MLLx versus CMP-MLLx.
  • Legends for data files S1 to S3
  • Reference (68)

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Other Supplementary Material for this manuscript includes the following:

  • Data file S1 (Microsoft Excel format). Tables S1 to S15.
  • Data file S2 (Microsoft Excel format). Raw data for Figs. 1 to 6.
  • Data file S3 (Microsoft Excel format). Raw data for figs. S1 to S12.