Quantitative assessment of the CD26+ leukemic stem cell compartment in chronic myeloid leukemia: patient-subgroups, prognostic impact, and technical aspects
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Martin Culen1,*, Marek Borsky1,2,*, Veronika Nemethova2,3, Filip Razga2,3, Jiri Smejkal2, Tomas Jurcek1,2, Dana Dvorakova1,2, Daniela Zackova1,2, Barbora Weinbergerova2, Lukas Semerad1,2, Irina Sadovnik4, Gregor Eisenwort4,5, Harald Herrmann4,5, Peter Valent4,5, Jiri Mayer1,2,6, Zdenek Racil1,2,6
1Department of Internal Medicine, Hematology and Oncology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
2Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic
3Polymer Institute of the Slovak Academy of Sciences, Bratislava, Slovak Republic
4Department of Internal Medicine I, Division of Haematology and Hemostaseology, Medical University of Vienna, Vienna, Austria
5Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria
6Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic
*These authors contributed equally to this work
Zdenek Racil, email: [email protected]
Keywords: CML, LSC, DPPIV/CD26, FISH, FACS
Received: December 17, 2015 Accepted: April 10, 2016 Published: April 29, 2016
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.
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