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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 |
Appears in Collections: | Elements Staff Publications |
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