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

Abstract

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.

The underestimated role of basophils in Ph+ chronic myeloid leukaemia

“…One critical molecule regarding LSC redistribution may be CD26, a surface enzyme (dipeptidyl‐deptidase IV = DPPIV) known to cleave SDF‐1 into inactive fragments. In CML, LSC themselves reportedly display CD26 72. Most other cell types in the normal BM and CML BM lack CD26.…”

“…The notion that basophils express substantial amounts of CD26 on their surface suggests that these cells may also be involved in SDF‐1 degradation and in the related migratory defect of CML LSC against this cytokine. Indeed, normal and CML stem cells express CXCR4, the receptor for SDF‐1; and disruption of SDF‐1 activity is considered to lead to stem cell mobilization 71, 72, 76, 77, 78. In this regard, it is worth noting that in patients with severe allergies where basophils may also increase, the numbers of circulating colony‐forming progenitor cells also increase 79.…”

The Vienna Cancer Stem Cell Club (VCSCC): First 10 Years and Future Perspectives

“…As assessed by gene chip and antibody-screen analyses, several new stem cell antigens, such as roundabout-4 (ROBO4), the IL-2 receptor alpha chain (CD25), dipeptidyl-peptidase IV (DPPIV = CD26), Siglec-3 (CD33) or Campath-1 (CD52), were identified in these studies [48][49][50][51][52][53][54]. An interesting observation was that in all overt leukemias, including even CLL, NSC reside within the CD34 + portion of the malignant clone.…”

“…In these analyses, several new important interactions have been discovered. An example is CD26, also known as di-deptidylpeptidase IV, an enzyme that degrades SDF-1-alpha and thereby disrupts specific interactions between CSC and the stem cell niche [52]. In addition, the VCSSC has a strong interest in epigenetic aspects of myeloid neoplasms and their LSC [54][55][56].…”

“…Major achievements include the development of theoretical concepts around CSC, the phenotypic characterization of CSC and LSC in various disease models, the identification of specific stem cell markers, the identification of molecular targets in neoplastic stem cells and the evaluation of drug responses. Putative LSC were identified in Ph + CML, CLL, MDS, AML, ALL, colon cancer and malignant melanoma [48][49][50][51][52][53][54].…”