MUC1 is a potential target for the treatment of acute myeloid leukemia stem cells

Cancer Res. 2013 Sep 1;73(17):5569-79. doi: 10.1158/0008-5472.CAN-13-0677. Epub 2013 Jul 18.


Acute myeloid leukemia (AML) is a malignancy of stem cells with an unlimited capacity for self-renewal. MUC1 is a secreted, oncogenic mucin that is expressed aberrantly in AML blasts, but its potential uses to target AML stem cells have not been explored. Here, we report that MUC1 is highly expressed on AML CD34(+)/lineage(-)/CD38(-) cells as compared with their normal stem cell counterparts. MUC1 expression was not restricted to AML CD34(+) populations as similar results were obtained with leukemic cells from patients with CD34(-) disease. Engraftment of AML stem cell populations that highly express MUC1 (MUC1(high)) led to development of leukemia in NOD-SCID IL2Rgamma(null) (NSG) immunodeficient mice. In contrast, MUC1(low) cell populations established normal hematopoiesis in the NSG model. Functional blockade of the oncogenic MUC1-C subunit with the peptide inhibitor GO-203 depleted established AML in vivo, but did not affect engraftment of normal hematopoietic cells. Our results establish that MUC1 is highly expressed in AML stem cells and they define the MUC1-C subunit as a valid target for their therapeutic eradication.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • ADP-ribosyl Cyclase 1 / genetics
  • ADP-ribosyl Cyclase 1 / metabolism
  • Animals
  • Antigens, CD34 / genetics
  • Antigens, CD34 / metabolism
  • Apoptosis / drug effects
  • Blotting, Western
  • Cell Differentiation
  • Cell Proliferation / drug effects
  • Female
  • Flow Cytometry
  • Humans
  • Immunoenzyme Techniques
  • Immunophenotyping
  • In Situ Hybridization, Fluorescence
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / pathology
  • Leukemia, Myeloid, Acute / prevention & control*
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Mucin-1 / chemistry
  • Mucin-1 / genetics
  • Mucin-1 / metabolism*
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Peptides / pharmacology*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction


  • (arginine)9-cysteinyl-glutaminyl-cysteinyl-arginyl-arginyl-lysyl-asparagine
  • Antigens, CD34
  • MUC1 protein, human
  • Mucin-1
  • Peptides
  • RNA, Messenger
  • ADP-ribosyl Cyclase 1