CD26/DPP-4 in Chronic Myeloid Leukemia.

Anna Sicuranza,Monica Bocchia,Donatella Raspadori

doi:10.3390/cancers14040891

Anna Sicuranza, Monica Bocchia + Show 1 more

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https://doi.org/10.3390/cancers14040891

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Abstract

Simple SummaryCD26/dipeptidylpeptidase IV (DPP-4) is a membrane-bound multifunctional protein expressed in many primary solid tumors and in hematological diseases. Recent investigations demonstrated its specific expression on leukemic stem cells (LSCs) of Chronic Myeloid Leukemia (CML) bone marrow (BM) and peripheral blood (PB) samples. Thanks to this evidence, CD26 has been considered a novel exclusive stem cell marker of CML. The aim of this review is to describe and analyze the role of CD26 in the context of hematological malignancies and specifically of CML and to highlight its potential clinical application for the management of this disease.CD26 expression is altered in many solid tumors and hematological malignancies. Recently, it has been demonstrated that it is a specific marker expressed on LSCs of CML, both in BM and PB samples, and absent on CD34+/CD38− stem cells in normal subjects or on LSCs of other myeloid neoplasms. CD26+ LSCs have been detected by flow-cytometry assays in all PB samples of Chronic-Phase CML patients evaluated at diagnosis. Additionally, it has been demonstrated that most CML patients undergoing Tyrosine Kinase Inhibitors (TKIs) treatment still harbored circulating measurable residual CD26+ LSCs, even when displaying a consistent deep molecular response without any significant association among the amounts of BCR-ABL transcript and CD26+ LSCs. Preliminary data of our Italian prospective multicenter study showed that CML patients with a poorer response presented with a higher number of CD26+ LSCs at diagnosis. These data confirmed that CD26 is a specific marker of CML and suggest that it could be considered for the monitoring of therapeutic responses.

Highlights

CD26/Dipeptidylpeptidase IV (DPP-4) is a 110 KDa type II glycoprotein
Experiments on CD26+ cell lines demonstrated that the Sezary syndrome (SS) cell’s chemiotaxis is influenced by soluble CD26: the presence or absence of sCD26 induces or inhibits the migratory response. These findings suggest that CD26 represents an important regulator of the SDF-1–CXCR4 axis by contributing to the SS cells recruitment in these patients [32]
It has been considered the possibility to employ the humanized IgG1 monoclonal antibody targeting CD26 to inhibit the human OC differentiation and to reduce the MM tumor burden. These results suggest that CD26 is a potential target molecule in MM and that huCD26mAb could act as a therapeutic agent [34]

Summary

Introduction

CD26/Dipeptidylpeptidase IV (DPP-4) is a 110 KDa type II glycoprotein. It is expressed both in soluble form in body fluids and as membrane-bound on the cell surface of several cells and tissues, in the kidney, small intestine, endothelial, epithelial cells, and immune system cells [1]. The CD26 protein structure consists of two subunits containing three domains: a catalytic region, a transmembrane region, and a large extracellular region (Figure 1). The activity of CD26 can occur through two different manners: an enzymaticdependent way or an enzymatic-independent action. CD26 digests and inactivates polypeptides, chemokines, and peptide hormones, such as the glucagonlike peptide or glucose-dependent insulinotropic peptide, whereas, for non-enzymatic action, it interacts with adenosine deaminase (ADA), caveolin-1 and other extracellular matrix (ECM) proteins

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