Hyperexpression of NOTCH-1 is found in immature acute myeloid leukemia.
The Notch signaling pathway is a cell program that is active during early development of multicellular organisms and is required for the formation of basic structures in the growing embryo. Scientific evidence which has accumulated during the last years clearly indicates that aberrant pathway activation may also be critical for the pathogenesis of malignant disease. Despite some limited information the exact role of the Notch signaling pathway in acute myeloid leukemia (AML) remains poorly defined. Immunohistochemical staining of paraffin-embedded bone marrow biopsies from 97 patients with AML, treated between February 1994 and May 2011, for NOTCH-1 was performed according to standardized procedures. Immunological, cytological, pathological, molecular and clinical data were obtained from the hospitals database and patient records. Hyperexpression of NOTCH-1 was seen in 7/97 AML specimens, the other patients showed some expression of NOTCH-1. There was a significant correlation between hyperexpression of NOTCH-1 and the morphological subgroup M0/1 - AML without morphologic maturation (p<0.001). Significant correlation between NOTCH-1 hyperexpression and coexpression of CD7, a phenotypic marker of immaturity (p<0.001) was also seen. Patients with hyperexpression of NOTCH-1 were found to have an inferior overall survival in this retrospective study. Our results indicate that a specific subgroup of AMLs may be associated with hyperexpression of components of the Notch signaling pathway. Better knowledge in pathway signaling in AML could help to identify patient subsets that may benefit from administration of pathway inhibitors and could also contribute to tailored treatment.
5th Department of Internal Medicine - Oncology/Hematology, Hospital Hietzing Vienna, Austria.
Thamer
T
Sliwa
University of Linköping Linköping, Sweden.
Sally
S
Awsa
Institute of Pathology, Hospital Hietzing Vienna, Austria.
Michael
M
Vesely
Institute of Pathology, Hospital Hietzing Vienna, Austria.
Doris
D
Rokitte
5th Department of Internal Medicine - Oncology/Hematology, Hospital Hietzing Vienna, Austria.
Peter
P
Grossschmidt
Institute of Laboratory Medicine, Hospital Hietzing Vienna, Austria.
Ruth
R
Jilch
Institute of Pathology, Hospital Hietzing Vienna, Austria.
Walter
W
Ulrich
5th Department of Internal Medicine - Oncology/Hematology, Hospital Hietzing Vienna, Austria ; Ludwig Boltzmann Institute for Clinical Oncology Vienna, Austria.
Klaus
K
Geissler
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D011379:Prognosis; D051881:Receptor, Notch1 / Q000378:metabolism*; D012189:Retrospective Studies; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation; D055815:Young Adult
D014408:Biomarkers, Tumor; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1
Acute myeloid leukemia; NOTCH-1; embryonic pathway