B Gerby,
E Clappier,
F Armstrong,
C Deswarte,
J Calvo,
S Poglio,
J Soulier,
N Boissel,
T Leblanc,
A Baruchel,
J Landman-Parker, P H Roméo,
P Ballerini,
F Pflumio
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ABSTRACT: Leukemia-initiating/repopulating cells (LICs), also named leukemic stem cells, are responsible for propagating human acute leukemia. Although they have been characterized in various leukemias, their role in T-cell acute lymphoblastic leukemia (T-ALL) is unclear. To identify and characterize LICs in T-ALL (T-LIC), we fractionated peripheral blood cell populations from patient samples by flow cytometry into three cell fractions by using two markers: CD34 (a marker of immature cells and LICs) and CD7 (a marker of early T-cell differentiation). We tested these populations in both in vitro culture assays and in vivo for growth and leukemia development in immune-deficient mice. We found LIC activity in CD7(+) cells only as CD34(+)CD7(-) cells contained normal human progenitors and hematopoietic stem cells that differentiated into T, B lymphoid and myeloid cells. In contrast, CD34(+)CD7(+) cells were enriched in LICs, when compared with CD34(-)CD7(+) cells. These CD34(+)CD7(+) cells also proliferated more upon NOTCH activation than CD34(-)CD7(+) cells and were sensitive to dexamethasone and NOTCH inhibitors. These data show that CD34 and CD7 expression in human T-ALL samples help in discriminating heterogeneous cell populations endowed with different LIC activity, proliferation capacity and responses to drugs.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 05/2011; 25(8):1249-58. · 8.30 Impact Factor
