PMID- 11806978
OWN - NLM
STAT- MEDLINE
DCOM- 20020306
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 99
IP  - 3
DP  - 2002 Feb 1
TI  - Stromal-derived factor 1 inhibits the cycling of very primitive human 
      hematopoietic cells in vitro and in NOD/SCID mice.
PG  - 792-9
AB  - Stromal-derived factor 1 (SDF-1) is a -CXC- chemokine that plays a critical role 
      in embryonic and adult hematopoiesis, and its specific receptor, CXCR4, has been 
      implicated in stem cell homing. In this study, it is shown that the addition of 
      SDF-1 to long-term cultures (LTCs) of normal human marrow can selectively, 
      reversibly, and specifically block the S-phase entry of primitive quiescent 
      erythroid and granulopoietic colony-forming cells (CFCs) present in the adherent 
      layer. Conversely, addition of anti-SDF-1 antibody or SDF-1(G2), a specific CXCR4 
      antagonist, to preactivated human LTCs prevented both types of primitive CFCs 
      from re-entering a quiescent state, demonstrating that endogenous SDF-1 
      contributes to the control of primitive CFC proliferation in the LTC system. 
      Interestingly, SDF-1 failed to arrest the proliferation of primitive chronic 
      myeloid leukemia CFCs in the adherent layer of LTCs containing normal marrow 
      stromal cells. In vivo, injection of SDF-1 arrested the cycling of normal human 
      LTC-initiating cells as well as primitive CFCs in the marrow of nonobese 
      diabetic/severe combined immunodeficient mice engrafted with human cord blood 
      cells. Conversely, injection of the antagonist, SDF-1(G2), reactivated the 
      cycling of quiescent primitive human CFCs present in the marrow of mice engrafted 
      with human marrow cells. These studies are the first to demonstrate a potential 
      physiological role of SDF-1 in regulating the cell-cycle status of primitive 
      hematopoietic cells and suggest that the deregulated cycling activity of 
      primitive chronic myeloid leukemia (CML) cells is due to the BCR-ABL-mediated 
      disruption of a pathway shared by multiple chemokine receptors.
FAU - Cashman, Johanne
AU  - Cashman J
AD  - Terry Fox Laboratory, British Columbia Cancer Agency, 601 West 10th Ave, 
      Vancouver, BC, V5Z 1L3, Canada.
FAU - Clark-Lewis, Ian
AU  - Clark-Lewis I
FAU - Eaves, Allen
AU  - Eaves A
FAU - Eaves, Connie
AU  - Eaves C
LA  - eng
GR  - P01 HL 55435/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (CXCL12 protein, human)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Chemokines, CXC)
RN  - 0 (Cxcl12 protein, mouse)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/cytology/drug effects
MH  - Bone Marrow Transplantation
MH  - Cell Cycle/drug effects
MH  - Cell Division/drug effects
MH  - Cells, Cultured
MH  - Chemokine CXCL12
MH  - Chemokines, CXC/administration & dosage/antagonists & inhibitors/*pharmacology
MH  - Fetal Blood/cytology/drug effects
MH  - Graft Survival/drug effects
MH  - Hematopoietic Stem Cells/*cytology/*drug effects
MH  - Humans
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology
MH  - Mice
MH  - Mice, Inbred NOD/*blood
MH  - Mice, SCID/*blood
MH  - Stem Cells/cytology/drug effects
MH  - Transplantation, Heterologous
EDAT- 2002/01/25 10:00
MHDA- 2002/03/07 10:01
CRDT- 2002/01/25 10:00
PHST- 2002/01/25 10:00 [pubmed]
PHST- 2002/03/07 10:01 [medline]
PHST- 2002/01/25 10:00 [entrez]
AID - S0006-4971(20)38268-9 [pii]
AID - 10.1182/blood.v99.3.792 [doi]
PST - ppublish
SO  - Blood. 2002 Feb 1;99(3):792-9. doi: 10.1182/blood.v99.3.792.