Notch Signaling Induces Apoptosis in Primary Human CD34+ Hematopoietic Progenitor Cells

Abstract

STEM CELLS 2007;25:203-210

Divergent effects of supraphysiologic Notch signals on leukemia stem cells and hematopoietic stem cells

“…Although in some studies authors suggested a positive effect, [27][28][29][30][31][32][41][42][43][44] other studies suggested a negative effect. 45,46 Our findings show that Notch stimulates murine HSPCs over the short term but over longer periods depletes this population. Thus, the positive effects of supraphysiologic Notch signaling observed in earlier studies may have been produced through effects on differentiated multipotential precursors rather than LT-HSCs, which are rare and difficult to study via use of the earlier 4-color flow cytometric techniques.…”

Searching for the Key to Expand Hematopoietic Stem Cells

“…In contrast to the murine studies, only a modest or no increase in the progenitor numbers was achieved by expressing activated Notch-1 in human CD34 + cord blood cells (Carlesso et al, 1999;Chadwick et al, 2007) or by incubation with Delta-1 (Jaleco et al, 2001), Delta-4 (Lauret et al, 2004) or Jagged-1 (Karanu et al, 2000;Karanu et al, 2001;Walker et al, 1999). This contrast with other reports showing that incubation of human cord blood cells with the immobilized Delta-1 combined with fibronectin fragments and cytokines induce a 100-fold increase in the number of CD34 + cells compare to controls (Ohishi et al, 2002) and a 16-fold increase in SCID Repopulating Cells (SRC) number compared to uncultured cells.…”

HES1 activation suppresses proliferation of leukemia cells in acute myeloid leukemia

“…In hematopoietic cells, Notch pathway plays either oncogenic or tumor suppressor roles, depending on the cell types [1][2][3]. In T cell acute lymphoblastic leukemia (T-ALL), Notch mutations are found in 50-70 % of patients [4].…”