Journal
ONCOTARGET
Volume 7, Issue 22, Pages 33016-33024Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.9108
Keywords
CML; LSC; DPPIV/CD26; FISH; FACS
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Funding
- Employment of Best Young Scientists for International Cooperation Empowerment - European Social Fund [CZ.1.07/2.3.00/30.0037]
- Czech Republic
- Austrian Science Fund [SFB F4704-B20]
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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. 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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