PMID- 27145281 OWN - NLM STAT- MEDLINE DCOM- 20180212 LR - 20221109 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 7 IP - 22 DP - 2016 May 31 TI - Quantitative assessment of the CD26+ leukemic stem cell compartment in chronic myeloid leukemia: patient-subgroups, prognostic impact, and technical aspects. PG - 33016-24 LID - 10.18632/oncotarget.9108 [doi] AB - 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. FAU - Culen, Martin AU - Culen M AD - Department of Internal Medicine, Hematology and Oncology, Faculty of Medicine, Masaryk University, Brno, Czech Republic. FAU - Borsky, Marek AU - Borsky M AD - Department of Internal Medicine, Hematology and Oncology, Faculty of Medicine, Masaryk University, Brno, Czech Republic. AD - Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic. FAU - Nemethova, Veronika AU - Nemethova V AD - Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic. AD - Polymer Institute of the Slovak Academy of Sciences, Bratislava, Slovak Republic. FAU - Razga, Filip AU - Razga F AD - Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic. AD - Polymer Institute of the Slovak Academy of Sciences, Bratislava, Slovak Republic. FAU - Smejkal, Jiri AU - Smejkal J AD - Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic. FAU - Jurcek, Tomas AU - Jurcek T AD - Department of Internal Medicine, Hematology and Oncology, Faculty of Medicine, Masaryk University, Brno, Czech Republic. AD - Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic. FAU - Dvorakova, Dana AU - Dvorakova D AD - Department of Internal Medicine, Hematology and Oncology, Faculty of Medicine, Masaryk University, Brno, Czech Republic. AD - Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic. FAU - Zackova, Daniela AU - Zackova D AD - Department of Internal Medicine, Hematology and Oncology, Faculty of Medicine, Masaryk University, Brno, Czech Republic. AD - Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic. FAU - Weinbergerova, Barbora AU - Weinbergerova B AD - Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic. FAU - Semerad, Lukas AU - Semerad L AD - Department of Internal Medicine, Hematology and Oncology, Faculty of Medicine, Masaryk University, Brno, Czech Republic. AD - Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic. FAU - Sadovnik, Irina AU - Sadovnik I AD - Department of Internal Medicine I, Division of Haematology and Hemostaseology, Medical University of Vienna, Vienna, Austria. FAU - Eisenwort, Gregor AU - Eisenwort G AD - Department of Internal Medicine I, Division of Haematology and Hemostaseology, Medical University of Vienna, Vienna, Austria. AD - Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria. FAU - Herrmann, Harald AU - Herrmann H AD - Department of Internal Medicine I, Division of Haematology and Hemostaseology, Medical University of Vienna, Vienna, Austria. AD - Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria. FAU - Valent, Peter AU - Valent P AD - Department of Internal Medicine I, Division of Haematology and Hemostaseology, Medical University of Vienna, Vienna, Austria. AD - Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria. FAU - Mayer, Jiri AU - Mayer J AD - Department of Internal Medicine, Hematology and Oncology, Faculty of Medicine, Masaryk University, Brno, Czech Republic. AD - Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic. AD - Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic. FAU - Racil, Zdenek AU - Racil Z AD - Department of Internal Medicine, Hematology and Oncology, Faculty of Medicine, Masaryk University, Brno, Czech Republic. AD - Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic. AD - Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic. LA - eng PT - Journal Article PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 RN - EC 3.4.14.5 (DPP4 protein, human) RN - EC 3.4.14.5 (Dipeptidyl Peptidase 4) SB - IM MH - Dipeptidyl Peptidase 4/*biosynthesis/immunology MH - Humans MH - Immunophenotyping MH - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/immunology/*pathology MH - Neoplastic Stem Cells/*immunology/pathology MH - Prognosis PMC - PMC5078071 OTO - NOTNLM OT - CML OT - DPPIV/CD26 OT - FACS OT - FISH OT - LSC COIS- P.V. has received research funding and honoraria from BMS, Novartis and Ariad. The other authors have no conflicts of interest to disclose in this study. EDAT- 2016/05/05 06:00 MHDA- 2018/02/13 06:00 PMCR- 2016/05/31 CRDT- 2016/05/05 06:00 PHST- 2015/12/17 00:00 [received] PHST- 2016/04/10 00:00 [accepted] PHST- 2016/05/05 06:00 [entrez] PHST- 2016/05/05 06:00 [pubmed] PHST- 2018/02/13 06:00 [medline] PHST- 2016/05/31 00:00 [pmc-release] AID - 9108 [pii] AID - 10.18632/oncotarget.9108 [doi] PST - ppublish SO - Oncotarget. 2016 May 31;7(22):33016-24. doi: 10.18632/oncotarget.9108.