Mucin1 expression is enriched in the human stem cell fraction of cord blood and is upregulated in majority of the AML cases

Exp Hematol. 2008 Oct;36(10):1254-65. doi: 10.1016/j.exphem.2008.04.015. Epub 2008 Jul 21.


Objective: Mucin1 is a membrane glycoprotein that is overexpressed in a variety of human cancers. Here, we analyzed the role of Mucin1 in human hematopoietic stem/progenitor cells as well as in acute myeloid leukemia (AML) cells.

Materials and methods: Mucin1 expression was determined within the normal stem cell and progenitor compartment, as well as in the AML CD34+ and CD34- subfractions of patient samples. Stem cells were enumerated in long-term culture-initiating cell (LTC-IC) assays in limiting dilution and progenitor frequencies in colony-forming cell (CFC) assays in methylcellulose, and consequences of elevated Mucin1 expression were studied using retroviral overexpression systems in cord blood (CB) CD34+ cells.

Results: Ten percent of CB and 5% of peripheral blood CD34+ cells expressed Mucin1. Retroviral overexpression of Mucin1 in CB CD34+ cells resulted in elevated stem cell and progenitor frequencies as determined in LTC-IC and CFC assays without affecting differentiation, which coincided with increased proliferation. Overexpression of intercellular adhesion molecule-1, a ligand for Mucin1, in MS5 stromal cells further increased LTC-IC frequencies. Mucin1 overexpression was associated with increased nuclear factor-kappaB p50 nuclear translocation, suggesting that Mucin1-induced phenotypes involve increased cell survival mechanisms. Finally, we observed increased Mucin1 expression in 70% of the AML cases (n=24), suggesting that elevated Mucin1 levels might be involved in regulating the proliferative potential of the immature leukemic compartment as well.

Conclusions: Our data indicate that hematopoietic stem cells as well as CD34+ AML subfractions are enriched for Mucin1 expression, and that overexpression of Mucin1 in CB cells is sufficient to increase both progenitor and LTC-IC frequencies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / analysis
  • Antigens, CD34 / analysis
  • Colony-Forming Units Assay
  • DNA Primers
  • Fetal Blood / physiology*
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Infant, Newborn
  • Intercellular Adhesion Molecule-1 / genetics
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / pathology
  • Mucin-1 / genetics*
  • Polymerase Chain Reaction
  • Retroviridae / genetics
  • Stem Cells / physiology*
  • Up-Regulation


  • Antigens, CD
  • Antigens, CD34
  • DNA Primers
  • MUC1 protein, human
  • Mucin-1
  • Intercellular Adhesion Molecule-1