Jagged-1: a new promising factor associated with favorable prognosis in patients with acute myeloid leukemia

Leuk Lymphoma. 2015 Feb;56(2):401-6. doi: 10.3109/10428194.2014.917638. Epub 2014 Jul 15.

Abstract

In this study Jagged-1 and Dll-1 surface expression as well as Notch-1 receptor intracellular domain (Notch-1-IC) expression were assessed by multi-color flow cytometry in leukemic blasts obtained from 88 patients with acute myeloid leukemia (AML). CD34+peripheral blood stem cells (PBSCs) were used as a control. The median expression of Jagged-1 and Dll-1 was significantly higher in AML blasts than in PBSCs (p=0.001 and p=0.002, respectively). Higher expression of Notch-1-IC was detected in patients with poor-risk karyotype as compared to good- and intermediate-risk groups (p=0.035). In our study, poor-risk cytogenetics and low (<median) expression of Jagged-1 were the only factors associated with significantly shorter overall survival in intensively treated patients according to multivariate analysis. In conclusion, high Jagged-1 surface level in leukemic cells is an independent favorable prognostic factor in patients with AML. To our knowledge, this is the first study evaluating the prognostic role of Notch-1-IC in AML blasts.

Keywords: Myeloid leukemias and dysplasias; prognostication; signaling therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Aged, 80 and over
  • Calcium-Binding Proteins / metabolism*
  • Female
  • Flow Cytometry / statistics & numerical data
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Jagged-1 Protein
  • Leukemia, Myeloid / diagnosis
  • Leukemia, Myeloid / metabolism*
  • Male
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Prognosis
  • Proportional Hazards Models
  • Receptor, Notch1 / metabolism
  • Serrate-Jagged Proteins
  • Survival Analysis
  • Young Adult

Substances

  • Calcium-Binding Proteins
  • DLK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • JAG1 protein, human
  • Jagged-1 Protein
  • Membrane Proteins
  • NOTCH1 protein, human
  • Receptor, Notch1
  • Serrate-Jagged Proteins