Blood Journal
Leading the way in experimental and clinical research in hematology

Leukemia initiating cells from some acute myeloid leukemia patients with mutated nucleophosmin reside in the CD34- fraction

  1. David C. Taussig1,*,
  2. Jacques Vargaftig2,
  3. Farideh Miraki-Moud1,
  4. Emmanuel Griessinger2,
  5. Kirsty Sharrock3,
  6. Tina Luke3,
  7. Debra Lillington1,
  8. Heather E. Oakervee1,
  9. Jamie Cavenagh1,
  10. Samir G. Agrawal1,
  11. T. Andrew Lister1,
  12. John G. Gribben1, and
  13. Dominique Bonnet2
  1. 1 CRUK Medical Oncology Unit, St. Bartholomew's hospital, Queen Mary University of London, London, United Kingdom;
  2. 2 Haematopoietic stem cell laboratory, Cancer Research UK London Research Institute, London, United Kingdom;
  3. 3 FACS laboratory, Cancer Research UK London Research Institute, London, United Kingdom
  1. * Corresponding author; email: d.taussig{at}


Leukemia initiating cells (LICs) in acute myeloid leukemia (AML) are believed to be restricted to the CD34+ fraction. However, one of the most frequently mutated genes in AML is nucleophosmin (NPM) and this is associated with low CD34 expression. We therefore investigated whether NPM mutated AMLs have LICs restricted to the CD34+ fraction. We transplanted sorted fractions of primary NPM mutated AML into immunodeficient mice to establish which fractions initiate leukemia. Approximately half of cases had LICs exclusively within the CD34- fraction while the CD34+ fraction contained normal multi-lineage hematopoietic repopulating cells. Most of the remaining cases had LICs in both CD34+ and CD34- fractions. When samples were sorted based on CD34 and CD38 expression multiple fractions initiated leukemia in primary and secondary recipients. The data indicate that the phenotype of LICs is more heterogeneous than previously realized and can vary even within a single sample. This feature of LICs may make them particularly difficult to eradicate using therapies targeted against surface antigens.

  • Submitted February 23, 2009.
  • Accepted December 1, 2009.