CD26/DPP-4 in Chronic Myeloid Leukemia

Simple Summary CD26/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.

Automated summary

CD26/DPP-4 is a membrane-bound multifunctional protein that is expressed in many solid tumors and hematological malignancies, and recent investigations have shown its specific expression on leukemic stem cells of Chronic Myeloid Leukemia. This finding suggests that CD26 could be a potential marker for monitoring therapeutic responses in CML patients receiving Tyrosine Kinase Inhibitors treatment. Preliminary data from a multicenter study in Italy indicated that CML patients with a poorer response had a higher number of CD26+ LSCs at diagnosis, confirming the specificity of CD26 as a marker in CML.