Quantitative assessment of the CD26+leukemic stem cell compartment in chronic myeloid leukemia: Patient-subgroups, prognostic impact, and technical aspects

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Authors

ČULEN Martin BORSKÝ Marek NÉMETHOVÁ Veronika RÁZGA Filip SMEJKAL Jiri JURČEK Tomáš DVOŘÁKOVÁ Dana ŽÁČKOVÁ Daniela WEINBERGEROVÁ Barbora SEMERÁD Lukáš SADOVNIK Irina EISENWORT Gregor HERRMANN Harald VALENT Peter MAYER Jiří RÁČIL Zdeněk

Year of publication 2016
Type Article in Periodical
Magazine / Source Oncotarget
MU Faculty or unit

Faculty of Medicine

Citation
Doi http://dx.doi.org/10.18632/oncotarget.9108
Field Oncology and hematology
Keywords CML; LSC; DPPIV/CD26; FISH; FACS
Attached files
Description 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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