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

Dipeptidylpeptidase IV (CD26) defines leukemic stem cells (LSC) in chronic myeloid leukemia

  1. Harald Herrmann1,
  2. Irina Sadovnik2,
  3. Sabine Cerny-Reiterer1,2,
  4. Thomas Rülicke3,
  5. Gabriele Stefanzl2,
  6. Michael Willmann4,
  7. Gregor Hoermann5,
  8. Martin Bilban5,
  9. Katharina Blatt2,
  10. Susanne Herndlhofer2,
  11. Matthias Mayerhofer5,
  12. Berthold Streubel6,
  13. Wolfgang R. Sperr1,2,
  14. Tessa L. Holyoake7,
  15. Christine Mannhalter5, and
  16. Peter Valent1,2
  1. 1Ludwig Boltzmann Cluster Oncology, and
  2. 2Department of Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, Vienna, Austria;
  3. 3Institute of Laboratory Animal Science and
  4. 4Department of Companion Animals and Horses, Clinic for Internal Medicine and Infectious Diseases, University of Veterinary Medicine Vienna, Vienna, Austria;
  5. 5Department of Laboratory Medicine, and
  6. 6Institute of Gynecology & Obstetrics, Medical University of Vienna, Vienna, Austria; and
  7. 7College of Medical, Veterinary & Life Sciences, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom

Key Points

  • DPPIV (CD26) is a new specific marker of CML LSC that aids CML diagnostics and the measurement, characterization, and purification of LSC.

  • DPPIV on CML LSC degrades SDF-1 and thereby promotes the niche-escape of LSC, which may contribute to extramedullary myeloproliferation in CML.


Chronic myeloid leukemia (CML) is a stem cell (SC) neoplasm characterized by the BCR/ABL1 oncogene. Although mechanisms of BCR/ABL1-induced transformation are well-defined, little is known about effector-molecules contributing to malignant expansion and the extramedullary spread of leukemic SC (LSC) in CML. We have identified the cytokine-targeting surface enzyme dipeptidylpeptidase-IV (DPPIV/CD26) as a novel, specific and pathogenetically relevant biomarker of CD34+/CD38 CML LSC. In functional assays, CD26 was identified as target enzyme disrupting the SDF-1-CXCR4-axis by cleaving SDF-1, a chemotaxin recruiting CXCR4+ SC. CD26 was not detected on normal SC or LSC in other hematopoietic malignancies. Correspondingly, CD26+ LSC decreased to low or undetectable levels during successful treatment with imatinib. CD26+ CML LSC engrafted NOD-SCID-IL-2Rγ−/− (NSG) mice with BCR/ABL1+ cells, whereas CD26 SC from the same patients produced multilineage BCR/ABL1 engraftment. Finally, targeting of CD26 by gliptins suppressed the expansion of BCR/ABL1+ cells. Together, CD26 is a new biomarker and target of CML LSC. CD26 expression may explain the abnormal extramedullary spread of CML LSC, and inhibition of CD26 may revert abnormal LSC function and support curative treatment approaches in this malignancy.

  • Submitted October 31, 2013.
  • Accepted April 16, 2014.
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