PMID- 17926185
OWN - NLM
STAT- MEDLINE
DCOM- 20080416
LR  - 20190116
IS  - 1029-2403 (Electronic)
IS  - 1026-8022 (Linking)
VI  - 49
IP  - 1
DP  - 2008 Jan
TI  - Chemotherapeutic treatment of bone marrow stromal cells strongly affects their 
      protective effect on acute myeloid leukemia cell survival.
PG  - 134-48
AB  - Bone marrow stromal cells (BMSCs) have been found to support leukemic cell 
      survival; however, the mechanisms responsible are far from elucidated yet. 
      Therefore, the effect of BMSCs on both proliferation and apoptosis 
      characteristics of acute myeloid leukaemia (AML) cells was investigated as well 
      as the effect of BMSCs exposure to chemotherapy on the stromal supportive 
      capacity. Leukemic HL-60 and primary AML cells were either untreated or treated 
      with cytarabine and subsequently cultured for 3-4 days, in the presence or 
      absence of untreated or cytarabine-treated BMSCs. The effect on proliferation and 
      apoptosis was investigated with flow cytometry using CFSE labeling and Syto16 and 
      7AAD staining. BMSCs were found to maintain cytarabine-exposed primary AML cells 
      by protection against spontaneous apoptosis. Accordingly, an increase in 
      phosphorylated-AKT and Bcl-2 expression was found. Concomitant exposure of BMSCs 
      to cytarabine resulted in a dose-dependent decrease of protective capacity of 
      BMSCs. Thus, inhibition of spontaneous apoptosis of leukemic cells mediated by 
      phosphorylation of AKT/Bcl-2 pathway results in protection of leukemic cells by 
      BMSCs, which decreases after BMSCs exposure to chemotherapy. Targeting both the 
      tumor cells and intervening in their interaction with the bone marrow 
      microenvironment may thus affect clinical outcome in AML.
FAU - Moshaver, Bijan
AU  - Moshaver B
AD  - Department of Hematology, VU University Medical Center, Amsterdam, The 
      Netherlands.
FAU - van der Pol, Marjolein A
AU  - van der Pol MA
FAU - Westra, August H
AU  - Westra AH
FAU - Ossenkoppele, Gert J
AU  - Ossenkoppele GJ
FAU - Zweegman, Sonja
AU  - Zweegman S
FAU - Schuurhuis, Gerrit Jan
AU  - Schuurhuis GJ
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Leuk Lymphoma
JT  - Leukemia & lymphoma
JID - 9007422
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 04079A1RDZ (Cytarabine)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
CIN - Leuk Lymphoma. 2008 Jan;49(1):17-8. PMID: 18203006
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis
MH  - *Bone Marrow
MH  - Cell Proliferation
MH  - Cell Survival/*drug effects
MH  - Cytarabine/pharmacology
MH  - Drug Design
MH  - Flow Cytometry
MH  - HL-60 Cells
MH  - Humans
MH  - Leukemia, Myeloid, Acute/*drug therapy/*pathology
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Stromal Cells/*drug effects/physiology
MH  - Tumor Cells, Cultured
EDAT- 2007/10/11 09:00
MHDA- 2008/04/17 09:00
CRDT- 2007/10/11 09:00
PHST- 2007/10/11 09:00 [pubmed]
PHST- 2008/04/17 09:00 [medline]
PHST- 2007/10/11 09:00 [entrez]
AID - 782925669 [pii]
AID - 10.1080/10428190701593636 [doi]
PST - ppublish
SO  - Leuk Lymphoma. 2008 Jan;49(1):134-48. doi: 10.1080/10428190701593636.