Zurück zur Übersicht
| Blood. 2014 Apr 28. pii: blood-2013-10-536078. doi: 10.1182/blood-2013-10-536078 |
| Dipeptidylpeptidase IV (CD26) defines leukemic stem cells (LSC) in chronic myeloid leukemia. |
| Herrmann H1, Sadovnik I2, Cerny-Reiterer S3, Rülicke T4, Stefanzl G5, Willmann M6, Hoermann G7, Bilban M8, Blatt K9, Herndlhofer S10, Mayerhofer M11, Streubel B12, Sperr WR13, Holyoake TL14, Mannhalter C15, Valent P16 |
 Author information
|
|
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. |
|
© 2014 by The American Society of Hematology. |
|
Publikations ID: 24778155 Quelle: öffnen |
Author information
Schnellinfo
-- Cancer Care
-- Kliniken und Partner
-- CCC Cancer School
-- Young CCC
-- CCC Tumorboards
-- CCC Forschungscluster
-- CCC Units
-- CCC Platforms
-- SOPs / Leitlinien
-- Kontakt
Featured
