|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
9
|
|
pubmed:dateCreated |
2003-9-1
|
|
pubmed:abstractText |
Bone-marrow minimal residual disease (MRD) causes relapse after chemotherapy in patients with acute myelogenous leukemia (AML). We postulate that the drug resistance is induced by the attachment of very late antigen (VLA)-4 on leukemic cells to fibronectin on bone-marrow stromal cells. We found that VLA-4-positive cells acquired resistance to anoikis (loss of anchorage) or drug-induced apoptosis through the phosphatidylinositol-3-kinase (PI-3K)/AKT/Bcl-2 signaling pathway, which is activated by the interaction of VLA-4 and fibronectin. This resistance was negated by VLA-4-specific antibodies. In a mouse model of MRD, we achieved a 100% survival rate by combining VLA-4-specific antibodies and cytosine arabinoside (AraC), whereas AraC alone prolonged survival only slightly. In addition, overall survival at 5 years was 100% for 10 VLA-4-negative patients and 44.4% for 15 VLA-4-positive patients. Thus, the interaction between VLA-4 on leukemic cells and fibronectin on stromal cells may be crucial in bone marrow MRD and AML prognosis.
|
|
pubmed:commentsCorrections |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/AKT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies,
http://linkedlifedata.com/resource/pubmed/chemical/Antimetabolites, Antineoplastic,
http://linkedlifedata.com/resource/pubmed/chemical/Cytarabine,
http://linkedlifedata.com/resource/pubmed/chemical/Fibronectins,
http://linkedlifedata.com/resource/pubmed/chemical/Integrin alpha4beta1,
http://linkedlifedata.com/resource/pubmed/chemical/Integrin alpha5beta1,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Sep
|
|
pubmed:issn |
1078-8956
|
|
pubmed:author |
pubmed-author:AkiyamaTakehideT,
pubmed-author:FujimiAkihitoA,
pubmed-author:HirayamaYasuoY,
pubmed-author:KatoJunjiJ,
pubmed-author:KawanoYutakaY,
pubmed-author:KobuneMasayoshiM,
pubmed-author:KohdaKyuheiK,
pubmed-author:KurodaHiroyukiH,
pubmed-author:MatsunagaTakuyaT,
pubmed-author:MiyakeKensukeK,
pubmed-author:NiitsuYoshiroY,
pubmed-author:SakamakiSumioS,
pubmed-author:SatoTsutomuT,
pubmed-author:TakemotoNaofumiN,
pubmed-author:TakimotoRishuR,
pubmed-author:TanakaIkutaI
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
9
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
1158-65
|
|
pubmed:dateRevised |
2010-11-18
|
|
pubmed:meshHeading |
pubmed-meshheading:12897778-Animals,
pubmed-meshheading:12897778-Antibodies,
pubmed-meshheading:12897778-Antimetabolites, Antineoplastic,
pubmed-meshheading:12897778-Cytarabine,
pubmed-meshheading:12897778-Drug Resistance, Neoplasm,
pubmed-meshheading:12897778-Fibronectins,
pubmed-meshheading:12897778-Humans,
pubmed-meshheading:12897778-Integrin alpha4beta1,
pubmed-meshheading:12897778-Integrin alpha5beta1,
pubmed-meshheading:12897778-Leukemia,
pubmed-meshheading:12897778-Leukemia, Myeloid, Acute,
pubmed-meshheading:12897778-Mice,
pubmed-meshheading:12897778-Mice, SCID,
pubmed-meshheading:12897778-Neoplasm, Residual,
pubmed-meshheading:12897778-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:12897778-Predictive Value of Tests,
pubmed-meshheading:12897778-Protein-Serine-Threonine Kinases,
pubmed-meshheading:12897778-Proto-Oncogene Proteins,
pubmed-meshheading:12897778-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:12897778-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:12897778-Signal Transduction,
pubmed-meshheading:12897778-Stromal Cells,
pubmed-meshheading:12897778-Survival Rate,
pubmed-meshheading:12897778-Time Factors,
pubmed-meshheading:12897778-Tumor Cells, Cultured
|
|
pubmed:year |
2003
|
|
pubmed:articleTitle |
Interaction between leukemic-cell VLA-4 and stromal fibronectin is a decisive factor for minimal residual disease of acute myelogenous leukemia.
|
|
pubmed:affiliation |
Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo 060-0061, Japan.
|
|
pubmed:publicationType |
Journal Article
|
