title: Quantitative assessment of the CD26+ leukemic stem cell compartment in chronic myeloid leukemia: patient-subgroups, prognostic impact, and technical aspects.
abstract: 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. In the current study, we investigated this marker in a cohort of 31 unselected CML patients. BCR/ABL1 positivity was analyzed in highly enriched stem cell fractions using fluorescence in situ hybridization (FISH) and reverse transcription PCR (RT-PCR). The proportion of CD26+ LSCs and CD26- HSCs varied considerably among the patients analyzed, and the percentage of CD26+ cells correlated with leukocyte count. The CD26 expression robustly discriminated LSCs from HSCs. This required a strict gating of the stem cell compartment. Thus, in patients with very low LSC or HSC numbers, only the highly sensitive RT-PCR method discriminated between clonal and non-clonal cells, while a robust FISH analysis required larger numbers of cells in both compartments. Finally, our data show that the numbers of CD26+ CML LSCs correlate with responses to treatment with BCR-ABL1 inhibitors.
authors.affiliation: Department of Internal Medicine, Hematology and Oncology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Culen
authors.affiliation: Department of Internal Medicine, Hematology and Oncology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.|Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic.
authors.forename: Marek
authors.initials: M
authors.lastname: Borsky
authors.affiliation: Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic.|Polymer Institute of the Slovak Academy of Sciences, Bratislava, Slovak Republic.
authors.forename: Veronika
authors.initials: V
authors.lastname: Nemethova
authors.affiliation: Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic.|Polymer Institute of the Slovak Academy of Sciences, Bratislava, Slovak Republic.
authors.forename: Filip
authors.initials: F
authors.lastname: Razga
authors.affiliation: Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Smejkal
authors.affiliation: Department of Internal Medicine, Hematology and Oncology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.|Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Jurcek
authors.affiliation: Department of Internal Medicine, Hematology and Oncology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.|Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic.
authors.forename: Dana
authors.initials: D
authors.lastname: Dvorakova
authors.affiliation: Department of Internal Medicine, Hematology and Oncology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.|Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic.
authors.forename: Daniela
authors.initials: D
authors.lastname: Zackova
authors.affiliation: Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic.
authors.forename: Barbora
authors.initials: B
authors.lastname: Weinbergerova
authors.affiliation: Department of Internal Medicine, Hematology and Oncology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.|Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic.
authors.forename: Lukas
authors.initials: L
authors.lastname: Semerad
authors.affiliation: Department of Internal Medicine I, Division of Haematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.
authors.forename: Irina
authors.initials: I
authors.lastname: Sadovnik
authors.affiliation: Department of Internal Medicine I, Division of Haematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.|Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria.
authors.forename: Gregor
authors.initials: G
authors.lastname: Eisenwort
authors.affiliation: Department of Internal Medicine I, Division of Haematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.|Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Herrmann
authors.affiliation: Department of Internal Medicine I, Division of Haematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.|Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
authors.affiliation: Department of Internal Medicine, Hematology and Oncology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.|Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic.|Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Mayer
authors.affiliation: Department of Internal Medicine, Hematology and Oncology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.|Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic.|Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic.
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Racil
mesh_terms: D018819:Dipeptidyl Peptidase 4 / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000276:immunology* / Q000473:pathology; D011379:Prognosis
chemical_list: C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4
keywords: CML; DPPIV/CD26; FACS; FISH; LSC