PMID- 9746772
OWN - NLM
STAT- MEDLINE
DCOM- 19981019
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 92
IP  - 7
DP  - 1998 Oct 1
TI  - MCP-1, not MIP-1alpha, is the endogenous chemokine that cooperates with TGF-beta 
      to inhibit the cycling of primitive normal but not leukemic (CML) progenitors in 
      long-term human marrow cultures.
PG  - 2338-44
AB  - The long-term culture (LTC) system has been useful for analyzing mechanisms by 
      which stromal cells regulate the proliferative activity of primitive normal, but 
      not chronic myeloid leukemia (CML), hematopoietic progenitor cells. In previous 
      studies, we identified two endogenous inhibitors in this system. One is 
      transforming growth factor-beta (TGF-beta), which is equally active on primitive 
      normal and CML progenitors. The other we now show to be monocyte chemoattractant 
      protein-1 (MCP-1). Thus, MCP-1, when added to LTC, blocked the activation of 
      primitive normal progenitors but did not arrest the cycling of primitive CML 
      progenitors. Moreover, the endogenous inhibitory activity of LTC stromal layers 
      could be overcome by the addition of neutralizing antibodies to MCP-1, but not to 
      macrophage inflammatory protein-1alpha (MIP-1alpha). However, neither of these 
      antibodies antagonized the inhibitory activity of NAc-Ser-Asp-Lys-Pro (AcSDKP) on 
      primitive normal but not CML progenitor cycling in this system. Moreover, none of 
      six other -C-C- or -C-X-C- chemokines, previously shown to inhibit primitive 
      normal human CFC proliferation in semisolid assays, were found to act as negative 
      regulators when added to normal LTC. These results provide further support for 
      the concept that primitive CML progenitor cell proliferation is deregulated when 
      these cells are exposed to limiting concentrations of multiple inhibitors, only 
      some of which have differential actions on normal and Ph+/BCR-ABL+ cells.
FAU - Cashman, J D
AU  - Cashman JD
AD  - Terry Fox Laboratory, British Columbia Cancer Agency and the Departments of 
      Medical Genetics, Medicine, and Pathology, University of British Columbia, 
      Vancouver, BC, Canada.
FAU - Eaves, C J
AU  - Eaves CJ
FAU - Sarris, A H
AU  - Sarris AH
FAU - Eaves, A C
AU  - Eaves AC
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL3)
RN  - 0 (Chemokine CCL4)
RN  - 0 (Cytokines)
RN  - 0 (Macrophage Inflammatory Proteins)
RN  - 0 (Oligopeptides)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Transforming Growth Factor beta)
RN  - EC 2.7.10.2 (Fusion Proteins, bcr-abl)
RN  - H041538E9P (goralatide)
SB  - IM
MH  - Bone Marrow/*pathology
MH  - Cell Cycle
MH  - Cell Division/drug effects
MH  - Cells, Cultured
MH  - Chemokine CCL2/pharmacology/*physiology
MH  - Chemokine CCL3
MH  - Chemokine CCL4
MH  - Cytokines/pharmacology
MH  - Fusion Proteins, bcr-abl/physiology
MH  - Hematopoiesis/drug effects/*physiology
MH  - Hematopoietic Stem Cells/cytology/*drug effects/physiology
MH  - Humans
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*pathology
MH  - Macrophage Inflammatory Proteins/pharmacology/*physiology
MH  - Neoplastic Stem Cells/*drug effects/pathology/physiology
MH  - Oligopeptides/pharmacology
MH  - Recombinant Proteins/pharmacology
MH  - Signal Transduction
MH  - Stromal Cells/physiology
MH  - Transforming Growth Factor beta/*physiology
MH  - Tumor Cells, Cultured
EDAT- 1998/09/25 00:00
MHDA- 1998/09/25 00:01
CRDT- 1998/09/25 00:00
PHST- 1998/09/25 00:00 [pubmed]
PHST- 1998/09/25 00:01 [medline]
PHST- 1998/09/25 00:00 [entrez]
AID - S0006-4971(20)74529-5 [pii]
PST - ppublish
SO  - Blood. 1998 Oct 1;92(7):2338-44.