title: Expression of CD34 and CD7 on human T-cell acute lymphoblastic leukemia discriminates functionally heterogeneous cell populations.
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.
authors.affiliation: Laboratoire des Cellules Souches Hématopoïétiques et Leucémiques, Institut de Radiobiologie Cellulaire et Moléculaire (IRCM), UMR967 INSERM, Université Paris 7, Fontenay-aux-Roses, France.
authors.forename: B
authors.initials: B
authors.lastname: Gerby
authors.forename: E
authors.initials: E
authors.lastname: Clappier
authors.forename: F
authors.initials: F
authors.lastname: Armstrong
authors.forename: C
authors.initials: C
authors.lastname: Deswarte
authors.forename: J
authors.initials: J
authors.lastname: Calvo
authors.forename: S
authors.initials: S
authors.lastname: Poglio
authors.forename: J
authors.initials: J
authors.lastname: Soulier
authors.forename: N
authors.initials: N
authors.lastname: Boissel
authors.forename: T
authors.initials: T
authors.lastname: Leblanc
authors.forename: A
authors.initials: A
authors.lastname: Baruchel
authors.forename: J
authors.initials: J
authors.lastname: Landman-Parker
authors.forename: P H
authors.initials: PH
authors.lastname: Roméo
authors.forename: P
authors.initials: P
authors.lastname: Ballerini
authors.forename: F
authors.initials: F
authors.lastname: Pflumio
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis*; D019011:Antigens, CD7 / Q000032:analysis*; D049109:Cell Proliferation; D003907:Dexamethasone / Q000494:pharmacology; D006410:Hematopoiesis; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D014411:Neoplastic Stem Cells / Q000473:pathology*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000473:pathology*; D051880:Receptors, Notch / Q000502:physiology; D015398:Signal Transduction
chemical_list: D018952:Antigens, CD34; D019011:Antigens, CD7; D051880:Receptors, Notch; D003907:Dexamethasone