PMID- 11480565
OWN - NLM
STAT- MEDLINE
DCOM- 20010816
LR  - 20190915
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 15
IP  - 8
DP  - 2001 Aug
TI  - Cell adhesion-mediated drug resistance (CAM-DR) protects the K562 chronic 
      myelogenous leukemia cell line from apoptosis induced by BCR/ABL inhibition, 
      cytotoxic drugs, and gamma-irradiation.
PG  - 1232-9
AB  - Integrin-mediated cellular adhesion to extracellular matrix (ECM) components is 
      an important determinant of chemotherapeutic response of human myeloma cells. 
      Here, we demonstrate that when K562 chronic myelogenous leukemia (CML) cells are 
      adhered to fibronectin (FN), they become resistant to apoptosis induced by the 
      BCR/ABL inhibitors AG957 and STI-571, as well as DNA damaging agents and 
      gamma-irradiation. This phenomenon, termed cell adhesion-mediated drug resistance 
      (CAM-DR), was induced by adhesion through the alpha5beta1 (VLA-5) integrin. 
      Phosphotyrosine analysis demonstrates that anti-apoptotic signaling through 
      integrins in K562 cells is independent of the tyrosine kinases activated by 
      BCR/ABL, with the possible exception of an unknown 80 kDa protein. Cytoprotection 
      of FN-adhered CML cells indicates that tumor-ECM interactions may be critical for 
      the emergence of drug-resistant tumor populations and treatment failure in this 
      disease. Antagonists of beta1 integrin-mediated adhesion or corresponding signal 
      transduction elements may sensitize CML cells to chemotherapy and prevent 
      resistance to the novel BCR/ABL kinase inhibitors being used for the treatment of 
      this disease.
FAU - Damiano, J S
AU  - Damiano JS
AD  - Department of Interdisciplinary Oncology, H Lee Moffitt Cancer Center and 
      Research Institute, University of South Florida Tampa 33612, USA.
FAU - Hazlehurst, L A
AU  - Hazlehurst LA
FAU - Dalton, W S
AU  - Dalton WS
LA  - eng
GR  - CA77859/CA/NCI NIH HHS/United States
GR  - CA82533/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Receptors, Fibronectin)
SB  - IM
MH  - Antineoplastic Agents/pharmacology/therapeutic use
MH  - Apoptosis/drug effects/*genetics/radiation effects
MH  - Cell Adhesion
MH  - Drug Resistance, Neoplasm
MH  - Genes, abl/*genetics
MH  - Humans
MH  - K562 Cells
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug 
      therapy/genetics/*pathology/radiotherapy
MH  - Receptors, Fibronectin/*genetics
MH  - Signal Transduction/genetics
EDAT- 2001/08/02 10:00
MHDA- 2001/08/17 10:01
CRDT- 2001/08/02 10:00
PHST- 2001/08/02 10:00 [pubmed]
PHST- 2001/08/17 10:01 [medline]
PHST- 2001/08/02 10:00 [entrez]
AID - 10.1038/sj.leu.2402179 [doi]
PST - ppublish
SO  - Leukemia. 2001 Aug;15(8):1232-9. doi: 10.1038/sj.leu.2402179.