Jagged-1: a new promising factor associated with favorable prognosis in patients with acute myeloid leukemia.
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.
Department of Hematology, Medical University of Lodz , Lodz , Poland.
Magdalena
M
Czemerska
Agnieszka
A
Pluta
Anna
A
Szmigielska-Kaplon
Ewa
E
Wawrzyniak
Barbara
B
Cebula-Obrzut
Aleksandra
A
Medra
Piotr
P
Smolewski
Tadeusz
T
Robak
Agnieszka
A
Wierzbowska
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry / Q000706:statistics & numerical data; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D000072100:Jagged-1 Protein; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D051881:Receptor, Notch1 / Q000378:metabolism; D000072099:Serrate-Jagged Proteins; D016019:Survival Analysis; D055815:Young Adult
D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D000072099:Serrate-Jagged Proteins
Myeloid leukemias and dysplasias; prognostication; signaling therapies