PMID- 10188883
OWN - NLM
STAT- MEDLINE
DCOM- 19990415
LR  - 20181113
IS  - 0007-0920 (Print)
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Linking)
VI  - 79
IP  - 9-10
DP  - 1999 Mar
TI  - Effects of bryostatin-1 on chronic myeloid leukaemia-derived haematopoietic 
      progenitors.
PG  - 1406-12
AB  - Bryostatin-1 belongs to the family of macrocyclic lactones isolated from the 
      marine bryozoan Bugula neritina and is a potent activator of protein kinase C 
      (PKC). Bryostatin has been demonstrated to possess both in vivo and in vitro 
      anti-leukaemic potential. In samples derived from chronic myeloid leukaemia (CML) 
      patients, it has been demonstrated that bryostatin-1 induces a macrophage 
      differentiation, suppresses colony growth in vitro and promotes cytokine 
      secretion from accessory cells. We investigated the effect of bryostatin-1 
      treatment on colony-forming unit-granulocyte macrophage (CFU-GM) capacity in the 
      presence of accessory cells, using mononuclear cells, as well as in the absence 
      of accessory cells using purified CD34-positive cells. Cells were obtained from 
      14 CML patients as well as from nine controls. Moreover, CD34-positive cells 
      derived from CML samples and controls were analysed for stem cell frequency and 
      ability using the long-term culture initiating cell (LTCIC) assay at limiting 
      dilution. Individual colonies derived from both the CFU-GM and LTCIC assays were 
      analysed for the presence of the bcr-abl gene with fluorescence in situ 
      hybridization (FISH) to evaluate inhibition of malignant colony growth. The 
      results show that at the CFU-GM level bryostatin-1 treatment resulted in only a 
      1.4-fold higher reduction of CML colony growth as compared to the control 
      samples, both in the presence and in the absence of accessory cells. However, at 
      the LTCIC level a sixfold higher reduction of CML growth was observed as compared 
      to the control samples. Analysis of the LTCICs at limiting dilution indicates 
      that this purging effect is caused by a decrease in output per malignant LTCIC 
      combined with an increase in the normal stem cell frequency. It is concluded that 
      bryostatin-1 selectively inhibits CML growth at the LTCIC level and should be 
      explored as a purging modality in CML.
FAU - Thijsen, S F
AU  - Thijsen SF
AD  - Department of Haematology, Free University Hospital, Amsterdam.
FAU - Schuurhuis, G J
AU  - Schuurhuis GJ
FAU - van Oostveen, J W
AU  - van Oostveen JW
FAU - Theijsmeijer, A P
AU  - Theijsmeijer AP
FAU - van der Hem, K G
AU  - van der Hem KG
FAU - Odding, J H
AU  - Odding JH
FAU - Drager, A M
AU  - Drager AM
FAU - Ossenkoppele, G J
AU  - Ossenkoppele GJ
LA  - eng
PT  - Journal Article
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Bryostatins)
RN  - 0 (Lactones)
RN  - 0 (Macrolides)
RN  - 37O2X55Y9E (bryostatin 1)
RN  - EC 2.7.10.2 (Fusion Proteins, bcr-abl)
SB  - IM
MH  - Antineoplastic Agents, Phytogenic/*pharmacology
MH  - Bryostatins
MH  - Enzyme Activation/drug effects
MH  - Fusion Proteins, bcr-abl/genetics
MH  - Granulocytes/cytology/*drug effects
MH  - Hematopoietic Stem Cells/*drug effects
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Lactones/*pharmacology
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*pathology
MH  - Macrolides
MH  - Macrophages/cytology/*drug effects
MH  - Tumor Stem Cell Assay
PMC - PMC2362710
EDAT- 1999/04/03 00:00
MHDA- 1999/04/03 00:01
CRDT- 1999/04/03 00:00
PHST- 1999/04/03 00:00 [pubmed]
PHST- 1999/04/03 00:01 [medline]
PHST- 1999/04/03 00:00 [entrez]
AID - 6690225 [pii]
AID - 10.1038/sj.bjc.6690225 [doi]
PST - ppublish
SO  - Br J Cancer. 1999 Mar;79(9-10):1406-12. doi: 10.1038/sj.bjc.6690225.