Acute B lymphoblastic leukaemia-propagating cells are present at high frequency in diverse lymphoblast populations.
Bottom Line: Here, we demonstrate in a wide range of primary patient samples and patient samples previously passaged through mice that leukaemia-propagating cells are found in all populations defined by high or low expression of the lymphoid differentiation markers CD10, CD20 or CD34.The frequency of leukaemia-propagating cells and their engraftment kinetics do not differ between these populations.Together, these findings suggest that there is no stem cell hierarchy in acute B lymphoblastic leukaemia.
Affiliation: Newcastle Cancer Centre at the Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.Show MeSH
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Mentions: The candidate gene we chose to test this hypothesis was TERT, encoding the reverse transcriptase protein subunit of telomerase. Telomerase restores telomeres and prevents replicative senescence. TERT protein supports the maintenance and expansion of normal and cancer stem cells both by telomerase-dependent and -independent mechanisms (Stewart et al, 2002). Moreover, our previous experiments showed that its expression is induced and maintained by key leukaemic fusion oncogenes, supporting its significant role in leukaemic propagation (Gessner et al, 2010). Unfortunately, the low expression levels of TERT may impede detection by gene expression arrays. We, therefore, analysed expression of TERT in CD34high and phenotypically more mature CD34low blasts using quantitative RT-PCR. In the absence of telomerase-independent alternative lengthening of telomeres, only blasts with TERT expression should possess the ability for long-term leukaemia propagation. As predicted, TERT mRNA levels in normal human umbilical cord blood were approximately five times higher in immature CD34high as compared with mature CD34low cells. In contrast, there were no differences in TERT expression between CD34high and CD34low leukaemic blasts (Fig 3A).
Affiliation: Newcastle Cancer Centre at the Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.