Coexistence of LMPP-like and GMP-like leukemia stem cells in acute myeloid leukemia.
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.
MRC MHU, WIMM, University of Oxford, Oxford OX3 9DS, UK.
Nicolas
N
Goardon
Emanuele
E
Marchi
Ann
A
Atzberger
Lynn
L
Quek
Anna
A
Schuh
Shamit
S
Soneji
Petter
P
Woll
Adam
A
Mead
Kate A
KA
Alford
Raj
R
Rout
Salma
S
Chaudhury
Amanda
A
Gilkes
Steve
S
Knapper
Kheira
K
Beldjord
Suriya
S
Begum
Susan
S
Rose
Nicola
N
Geddes
Mike
M
Griffiths
Graham
G
Standen
Alexander
A
Sternberg
Jamie
J
Cavenagh
Hannah
H
Hunter
David
D
Bowen
Sally
S
Killick
Lisa
L
Robinson
Andrew
A
Price
Elizabeth
E
Macintyre
Paul
P
Virgo
Alan
A
Burnett
Charles
C
Craddock
Tariq
T
Enver
Sten Eirik W
SE
Jacobsen
Catherine
C
Porcher
Paresh
P
Vyas
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D020869:Gene Expression Profiling; D006085:Graft Survival; D055014:Granulocyte-Macrophage Progenitor Cells / Q000166:cytology* / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism / Q000473:pathology*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D054503:Lymphoid Progenitor Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology* / Q000637:transplantation; D014183:Transplantation, Heterologous / Q000473:pathology; D055815:Young Adult
D015703:Antigens, CD; D018952:Antigens, CD34; D017493:Leukocyte Common Antigens