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Little is known about the function and phenotype of leukemic stem cells (LSCs) in chronic myeloid leukemia (CML) or about specific markers that discriminate LSCs from normal hematopoietic stem cells (HSCs). CD26 has recently been described as a specific marker of CML LSCs.

Current research in CML has focused on the identification and characterization of LSCs. This might enable eradication of LSCs and provide a curative therapy in CML. However, the identification of LSCs and their separation from normal hematopoietic stem cells (HSCs) in CML is challenging, since both populations reside in the same compartment phenotypically defined as CD45+34+38–. Recently, several groups have reported on more or less specific LSC markers and LSC-related light scatter properties in CML. One of such markers appears to be IL-1RAP, while another is CD26, which is also known as dipeptidylpeptidase IV (DPPIV). This functionally relevant cell surface antigen as well as IL-1RAP is specifically expressed on CML LSCs, but not on HSCs. LSC-specific markers, such as IL-1RAP or CD26, may also represent suitable targets for anti-LSC therapy as well as potential prognostic markers. More recent data suggest that the levels of CD26 on CML LSCs may vary from patient to patient.

…we confirmed that CD26 staining can accurately discriminate between LSCs and HSCs in all CML CP patients, which is of great clinical and diagnostic value. Additional studies are now required to determine whether the percentage of CD26+ SCs and the LSC/HSC proportion is of prognostic significance regarding survival and progression-free survival. In addition, further studies will be required to explore whether LSC phenotyping can be employed as a follow-up parameter in poorly responding or relapsing patients….

Culen M, Borsky M, Nemethova V et al. Quantitative assessment of the CD26+ leukemic stem cell compartment in chronic myeloid leukemia: patient-subgroups, prognostic impact, and technical aspects. Oncotarget. 2016, 7: 33016-33024

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