PMID- 21157036
OWN - NLM
STAT- MEDLINE
DCOM- 20110203
LR  - 20211020
IS  - 1558-8238 (Electronic)
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 121
IP  - 1
DP  - 2011 Jan
TI  - Human acute myelogenous leukemia stem cells are rare and heterogeneous when 
      assayed in NOD/SCID/IL2Rgammac-deficient mice.
PG  - 384-95
LID - 41495 [pii]
LID - 10.1172/JCI41495 [doi]
AB  - Human leukemic stem cells, like other cancer stem cells, are hypothesized to be 
      rare, capable of incomplete differentiation, and restricted to a phenotype 
      associated with early hematopoietic progenitors or stem cells. However, recent 
      work in other types of tumors has challenged the cancer stem cell model. Using a 
      robust model of xenotransplantation based on NOD/SCID/IL2Rgammac-deficient mice, we 
      confirmed that human leukemic stem cells, functionally defined by us as SCID 
      leukemia-initiating cells (SL-ICs), are rare in acute myelogenous leukemia (AML). 
      In contrast to previous results, SL-ICs were found among cells expressing lineage 
      markers (i.e., among Lin+ cells), CD38, or CD45RA, all markers associated with 
      normal committed progenitors. Remarkably, each engrafting fraction consistently 
      recapitulated the original phenotypic diversity of the primary AML specimen and 
      contained self-renewing leukemic stem cells, as demonstrated by secondary 
      transplants. While SL-ICs were enriched in the Lin-CD38- fraction compared with 
      the other fractions analyzed, SL-ICs in this fraction represented only one-third 
      of all SL-ICs present in the unfractionated specimen. These results indicate that 
      human AML stem cells are rare and enriched but not restricted to the phenotype 
      associated with normal primitive hematopoietic cells. These results suggest a 
      plasticity of the cancer stem cell phenotype that we believe has not been 
      previously described.
FAU - Sarry, Jean-Emmanuel
AU  - Sarry JE
AD  - Division of Hematology and Oncology, Department of Medicine, University of 
      Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
FAU - Murphy, Kathleen
AU  - Murphy K
FAU - Perry, Robin
AU  - Perry R
FAU - Sanchez, Patricia V
AU  - Sanchez PV
FAU - Secreto, Anthony
AU  - Secreto A
FAU - Keefer, Cathy
AU  - Keefer C
FAU - Swider, Cezary R
AU  - Swider CR
FAU - Strzelecki, Anne-Claire
AU  - Strzelecki AC
FAU - Cavelier, Cindy
AU  - Cavelier C
FAU - Recher, Christian
AU  - Recher C
FAU - Mansat-De Mas, Veronique
AU  - Mansat-De Mas V
FAU - Delabesse, Eric
AU  - Delabesse E
FAU - Danet-Desnoyers, G
AU  - Danet-Desnoyers G
FAU - Carroll, Martin
AU  - Carroll M
LA  - eng
GR  - K01 CA129151/CA/NCI NIH HHS/United States
GR  - K12CA07693/CA/NCI NIH HHS/United States
GR  - KO1-CA-129151-01/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20101213
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (DNA Primers)
RN  - 0 (Il2rg protein, mouse)
RN  - 0 (Interleukin Receptor Common gamma Subunit)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Cell Differentiation
MH  - Cell Lineage
MH  - DNA Primers/genetics
MH  - Female
MH  - Hematopoietic Stem Cells/pathology
MH  - Humans
MH  - Immunophenotyping
MH  - Interleukin Receptor Common gamma Subunit/deficiency/genetics
MH  - Leukemia, Myeloid, Acute/genetics/*pathology/physiopathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, Knockout
MH  - Mice, SCID
MH  - Models, Biological
MH  - Neoplastic Stem Cells/*pathology/physiology/*transplantation
MH  - Transplantation, Heterologous
PMC - PMC3007135
EDAT- 2010/12/16 06:00
MHDA- 2011/02/04 06:00
PMCR- 2010/12/13
CRDT- 2010/12/16 06:00
PHST- 2009/10/19 00:00 [received]
PHST- 2010/10/28 00:00 [accepted]
PHST- 2010/12/16 06:00 [entrez]
PHST- 2010/12/16 06:00 [pubmed]
PHST- 2011/02/04 06:00 [medline]
PHST- 2010/12/13 00:00 [pmc-release]
AID - 41495 [pii]
AID - 10.1172/JCI41495 [doi]
PST - ppublish
SO  - J Clin Invest. 2011 Jan;121(1):384-95. doi: 10.1172/JCI41495. Epub 2010 Dec 13.