title: Prognostic impact of δ-like ligand 4 and Notch1 in acute myeloid leukemia.
abstract: Notch signaling plays a critical role in embryonic vascular development             and tumor angiogenesis. The present study was conducted to investigate the prognostic             role of the angiogenesis-related Notch ligand and the receptor in acute myeloid             leukemia (AML) and assess whether their expression correlates with that of the             vascular endothelial growth factor (VEGF) and angiopoietin (Ang)-2. Bone marrow             mononuclear cells from 60 untreated AML patients and 40 healthy controls were             obtained. Real-time RT-PCR was performed to evaluate the mRNA expression of δ-like             ligand 4 (Dll4), Notch1, VEGF, VEGF receptor (VEGFR)-1, VEGFR-2, Ang-1, Ang-2             and Tie2. Western blot analysis was used to determine the protein levels of Dll4             and Notch1. The results demonstrated that Dll4, Notch1, VEGF, VEGFR-2 and Ang-2             expression were significantly higher in untreated AML patients than in the controls.             Univariate analysis of factors associated with the overall survival showed a significantly             shorter survival in patients with the unfavorable karyotype, higher Dll4 expression,             higher Notch1 expression, higher VEGF expression or higher Ang-2 expression. Furthermore,             multivariate analysis revealed that the karyotype and expression levels of Notch1,             Dll4, VEGF and Ang-2 were independent prognostic factors for overall survival.             Additionally, the prognostic value of Dll4 expression (but not Notch1) was more             significant in the subgroup consisting of patients with intermediate-risk cytogenetics.             Subgroup analysis showed that Notch1 and Dll4 expression levels had a prognostic             impact on patients with high VEGF or Ang-2 levels. Taken together, our data provide             evidence that the activation of the Notch pathway may indicate an unfavorable             prognosis in AML. In particular, Dll4 may be a relevant prognostic marker in intermediate-risk             AML.
authors.affiliation: Department of Hematology, Qilu Hospital, Shandong University, Jinan, PR China.
authors.forename: Jingru
authors.initials: J
authors.lastname: Zhang
authors.forename: Daoxin
authors.initials: D
authors.lastname: Ma
authors.forename: Jingjing
authors.initials: J
authors.lastname: Ye
authors.forename: Shaolei
authors.initials: S
authors.lastname: Zang
authors.forename: Fei
authors.initials: F
authors.lastname: Lu
authors.forename: Meixiang
authors.initials: M
authors.lastname: Yang
authors.forename: Xun
authors.initials: X
authors.lastname: Qu
authors.forename: Xiulian
authors.initials: X
authors.lastname: Sun
authors.forename: Chunyan
authors.initials: C
authors.lastname: Ji
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D000368:Aged; D042702:Angiopoietin-2 / Q000235:genetics; D002135:Calcium-Binding Proteins; D016022:Case-Control Studies; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics; D011379:Prognosis; D051881:Receptor, Notch1 / Q000235:genetics* / Q000378:metabolism; D042787:Receptor, TIE-2 / Q000235:genetics; D059467:Transcriptome; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D042702:Angiopoietin-2; D002135:Calcium-Binding Proteins; C424126:DLL4 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2