Ubiquitin-proteasome system profiling in acute leukemias and its clinical relevance.
The ubiquitin-proteasome system (UPS) plays a major role in the homeostasis of cellular protein. We demonstrate that each of the major hematologic diseases (AML, ALL, and MDS) has a specific and different plasma profile of UPS protein and enzymatic activities. While high levels of proteasome and ubiquitin proteins and enzymatic activities are detected in the plasma samples from patients, normalizing enzymatic activities, show that each proteasome has lower enzymatic activities in these diseases as compared with normal controls. Proteasome protein levels in AML are strong predictor of survival independently of cytogenetics, performance status and age. The Ch-L activity when normalized to the level of proteasome protein show significant negative correlation with survival in ALL.
Department of Hematopathology, Quest Diagnostics Nichols Institute, 33608 Ortega Highway, San Juan Capistrano, CA 92675, USA.
Wanlong
W
Ma
Hagop
H
Kantarjian
Xi
X
Zhang
Xiuiang
X
Wang
Zeev
Z
Estrov
Susan
S
O'Brien
Maher
M
Albitar
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000097:blood* / Q000473:pathology; D008875:Middle Aged; D015999:Multivariate Analysis; D009190:Myelodysplastic Syndromes / Q000097:blood* / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood* / Q000473:pathology; D011379:Prognosis; D046988:Proteasome Endopeptidase Complex / Q000097:blood*; D025801:Ubiquitin / Q000097:blood*; D055815:Young Adult
D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex