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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.

Type

Journal

Cancer cell

Publication Date

01/2011

Volume

19

Pages

138 - 152

Addresses

MRC MHU, WIMM, University of Oxford, Oxford OX3 9DS, UK.

Keywords

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