Herrmann, H. et al. (2014) Dipeptidylpeptidase IV (CD26) defines leukemic stem cells (LSC) in chronic myeloid leukemia. Blood, 123(25), pp. 3951-3962. (doi: 10.1182/blood-2013-10-536078) (PMID:24778155)
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Abstract
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.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Holyoake, Professor Tessa |
| Authors: | Herrmann, H., Sadovnik, I., Cerny-Reiterer, S., Rulicke, T., Stefanzl, G., Willmann, M., Hoermann, G., Bilban, M., Blatt, K., Herndlhofer, S., Mayerhofer, M., Streubel, B., Sperr, W. R., Holyoake, T. L., Mannhalter, C., and Valent, P. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | Blood |
| Publisher: | American Society of Hematology |
| ISSN: | 0006-4971 |
| ISSN (Online): | 1528-0020 |
| Copyright Holders: | Copyright © 2014 American Society of Hematology |
| First Published: | First published in Blood 123(25):3951-3962 |
| Publisher Policy: | Reproduced in accordance with the copyright policy of the publisher. |
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