DPPIV (CD26) as a novel stem cell marker in Ph+ chronic myeloid leukaemia

Abstract

The concept of leukaemic stem cells (LSCs) has been developed to explain the complex cellular hierarchy and biology of leukaemias and to screen for pivotal targets that can be employed to improve drug therapies through LSC eradication in these patients. Some of the newly discovered LSC markers seem to be expressed in a disease-specific manner and may thus serve as major research tools and diagnostic parameters. A useful LSC marker in chronic myeloid leukaemia (CML) appears to be CD26, also known as dipeptidylpeptidase IV. Expression of CD26 is largely restricted to CD34 + /CD38 À LSCs in BCR/ABL1 + CML, but is not found on LSCs in other myeloid or lymphoid neoplasms, with the exception of lymphoid blast crisis of CML, BCR/ABL1 p210 + acute lymphoblastic leukaemia, and a very few cases of acute myeloid leukaemia. Moreover, CD26 usually is not expressed on normal bone marrow (BM) stem cells. Functionally, CD26 is a cytokine-targeting surface enzyme that may facilitate the mobilization of LSCs from the BM niche. In this article, we review our current knowledge about the biology and function of CD26 on CML LSCs and discuss the diagnostic potential of this new LSC marker in clinical haematology.

Quantitative assessment of the CD26+ leukemic stem cell compartment in chronic myeloid leukemia: patient-subgroups, prognostic impact, and technical aspects

“…In regard to prognostic scores, Janssen et al found that patients with residual HSCs showed significantly better EUTOS and EURO-scores [15]. In contrast, we found no such relationship for our 3 groups, and similarly no correlation was previously found when considering only the percentage of CD26 + SCs [17]. …”

“…Recently, Herrmann et al analyzed various surface antigens that were formerly hypothesized to define CML LSCs [17]. CD26 was reported to provide the highest specificity, which was confirmed by a series of thorough experiments including long-term culture-initiating cell (LTC-IC) and xenotransplantation assays.…”

“…This functionally relevant cell surface antigen as well as IL-1RAP is specifically expressed on CML LSCs, but not on HSCs [10]. LSC-specific markers, such as IL-1RAP or CD26, may also represent suitable targets for anti-LSC therapy as well as potential prognostic markers [17]. More recent data suggest that the levels of CD26 on CML LSCs may vary from patient to patient [10, 17].…”

“…LSC-specific markers, such as IL-1RAP or CD26, may also represent suitable targets for anti-LSC therapy as well as potential prognostic markers [17]. More recent data suggest that the levels of CD26 on CML LSCs may vary from patient to patient [10, 17]. The aim of this study was to investigate whether CD26 + LSC and CD26 − HSC populations can be identified and discriminated from each other in an unselected cohort of patients with de novo chronic phase (CP) CML.…”

CD26 a cancer stem cell marker and therapeutic target

“…Besides, an increase in CD26 expression was also observed, which was confirmed by the qPCR technique [25]. This result was also confirmed in another study with LSC, where CD26 showed high expression together with BCR/ABL1, an oncoprotein considered essential for CML manifestation [20,33].…”