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The relationships between normal and leukemic stem/progenitor cells are unclear. We show that in ∼80% of primary human CD34+ acute myeloid leukemia (AML), two expanded populations with hemopoietic progenitor immunophenotype coexist in most patients. Both populations have leukemic stem cell (LSC) activity and are hierarchically ordered; one LSC population gives rise to the other. Global gene expression profiling shows the LSC populations are molecularly distinct and resemble normal progenitors but not stem cells. The more mature LSC population most closely mirrors normal granulocyte-macrophage progenitors (GMP) and the immature LSC population a previously uncharacterized progenitor functionally similar to lymphoid-primed multipotential progenitors (LMPPs). This suggests that in most cases primary CD34+ AML is a progenitor disease where LSCs acquire abnormal self-renewal potential.

Original publication

DOI

10.1016/j.ccr.2010.12.012

Type

Journal article

Journal

Cancer Cell

Publication Date

18/01/2011

Volume

19

Pages

138 - 152

Keywords

Adult, Aged, Aged, 80 and over, Animals, Antigens, CD, Antigens, CD34, Antigens, CD45, Cell Differentiation, Cell Lineage, Gene Expression Profiling, Graft Survival, Granulocyte-Macrophage Progenitor Cells, Hematopoietic Stem Cells, Humans, Immunophenotyping, Leukemia, Myeloid, Acute, Lymphoid Progenitor Cells, Mice, Mice, Inbred NOD, Mice, SCID, Middle Aged, Neoplastic Stem Cells, Transplantation, Heterologous, Young Adult