Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41408-018-0134-z
Title: Low-level expression of SAMHD1 in acute myeloid leukemia (AML) blasts correlates with improved outcome upon consolidation chemotherapy with high-dose cytarabine-based regimens
Authors: Rassidakis, G.Z
Herold, N
Myrberg, I.H
Tsesmetzis, N
Rudd, S.G
Henter, J.-I
Schaller, T
Ng, S.-B 
Chng, W.J 
Yan, B
Ng, C.H 
Ravandi, F
Andreeff, M
Kantarjian, H.M
Medeiros, L.J
Xagoraris, I
Khoury, J.D
Keywords: cladribine
clofarabine
cytarabine
deoxynucleoside triphosphate triphosphohydrolase SAMHD1
DNA methyltransferase 3A
fludarabine
gemtuzumab ozogamicin
sorafenib
vorinostat
antineoplastic agent
cytarabine
deoxynucleoside triphosphate triphosphohydrolase SAMHD1
SAMHD1 protein, human
tumor marker
acute myeloid leukemia
adult
aged
allogeneic stem cell transplantation
Article
blood
bone marrow
cancer patient
clinical outcome
cohort analysis
consolidation chemotherapy
controlled study
de novo acute myeloid leukemia
drug megadose
event free survival
female
follow up
high risk population
human
immunohistochemistry
induction chemotherapy
leukocyte count
low drug dose
major clinical study
male
megakaryocyte
protein expression
tissue microarray
very elderly
acute myeloid leukemia
adolescent
consolidation chemotherapy
gene expression regulation
genetics
Kaplan Meier method
metabolism
middle aged
mortality
multimodality cancer therapy
pathology
prognosis
proportional hazards model
young adult
Adolescent
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
Biomarkers, Tumor
Bone Marrow
Combined Modality Therapy
Consolidation Chemotherapy
Cytarabine
Female
Gene Expression Regulation, Leukemic
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Leukemia, Myeloid, Acute
Male
Middle Aged
Prognosis
Proportional Hazards Models
SAM Domain and HD Domain-Containing Protein 1
Young Adult
Issue Date: 2018
Publisher: Nature Publishing Group
Citation: Rassidakis, G.Z, Herold, N, Myrberg, I.H, Tsesmetzis, N, Rudd, S.G, Henter, J.-I, Schaller, T, Ng, S.-B, Chng, W.J, Yan, B, Ng, C.H, Ravandi, F, Andreeff, M, Kantarjian, H.M, Medeiros, L.J, Xagoraris, I, Khoury, J.D (2018). Low-level expression of SAMHD1 in acute myeloid leukemia (AML) blasts correlates with improved outcome upon consolidation chemotherapy with high-dose cytarabine-based regimens. Blood Cancer Journal 8 (11) : 98. ScholarBank@NUS Repository. https://doi.org/10.1038/s41408-018-0134-z
Abstract: Sterile alpha motif and histidine/aspartic acid domain containing protein 1 (SAMHD1) limits the efficacy of cytarabine (ara-C) used in AML by hydrolyzing its active metabolite ara-CTP and thus represents a promising therapeutic target. SAMHD1 has also been implicated in DNA damage repair that may impact DNA damage-inducing therapies such as anthracyclines, during induction therapy. To determine whether SAMHD1 limits ara-C efficacy during induction or consolidation therapy, SAMHD1 protein levels were assessed in two patient cohorts of de novo AML from The University of Texas MD Anderson Cancer Center (USA) and the National University Hospital (Singapore), respectively, using immunohistochemistry and tissue microarrays. SAMHD1 was expressed at a variable level by AML blasts but not in a broad range of normal hematopoietic cells in reactive bone marrows. A sizeable patient subset with low SAMHD1 expression (<25% of positive blasts) was identified, which was significantly associated with longer event-free (EFS) and overall (OS) survival in patients receiving high-dose cytarabine (HDAC) during consolidation. Therefore, evaluation of SAMHD1 expression level in AML blasts at diagnosis, may stratify patient groups for future clinical trials combining HDAC with novel SAMHD1 inhibitors as consolidation therapy. © 2018, The Author(s).
Source Title: Blood Cancer Journal
URI: https://scholarbank.nus.edu.sg/handle/10635/174354
ISSN: 2044-5385
DOI: 10.1038/s41408-018-0134-z
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