Stabilization of SAMHD1 by NONO is crucial for Ara-C resistance in AML

Zhang, Feifei; Sun, Jun; Tang, Xiaofeng; Liang, Yiping; Jiao, QuanHui; Yu, Bo; Dai, Zhengzai; Yuan, Xuhui; Li, Jiayu; Yan, Jin-Hua; Zhang, Zhiping; Fan, ST; Wang, Min; Hu, Haiyan; Zhang, Changhua; Lv, Xiao-Bin

doi:10.1038/s41419-022-05023-0

Cited by 13 publications

(8 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When restricting to patients who received high-dose Ara-C (HDAC) in consolidation therapy, significant association between SAMHD1 levels and EFS and OS was observed, implying SAMHD1’s significance during postremission consolidation therapies. Recently, a study by Zhang et al 28 showed that non-POU domain–containing octamer-binding protein (NONO) interacts with, and stabilizes, SAMHD1 in AML cell lines and in an AML xenograft model. Interestingly, this study confirmed that SAMHD1 protein level expression was positively correlated with NONO protein levels in THP-1 and HL60 cells; however, association with NONO and SAMHD1 mRNA levels were not observed, thus indicating posttranslational regulation of SAMHD1.…”

Section: Discussionmentioning

confidence: 99%

SAMHD1 single nucleotide polymorphisms impact outcome in children with newly diagnosed acute myeloid leukemia

Marrero

Cao

et al. 2023

Blood Advances

View full text Add to dashboard Cite

Cytarabine arabinoside (Ara-C) has been the cornerstone of AML chemotherapy for decades. Following cellular uptake, it is phosphorylated into its active triphosphate form (Ara-CTP), which primarily exerts its cytotoxic effects by inhibiting DNA synthesis in proliferating cells. Interpatient variation in the enzymes involved in the Ara-C metabolic pathway have been shown to impact intracellular abundance of Ara-CTP and thus its therapeutic benefit. Recently, SAMHD1 (SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1) has emerged to play a role in Ara-CTP inactivation, development of drug resistance and consequently, clinical response in AML. Despite this the impact of genetic variations in SAMHD1 on outcome in AML has not been investigated in depth. In this study, we evaluated 25 single nucleotide polymorphisms (SNPs) within SAMHD1 gene for association with clinical outcome in 400 newly diagnosed pediatric AML patients from two clinical trials- AML02 and AML08. Three SNPs, rs1291128, rs1291141, and rs7265241 located in the 3' region of SAMHD1 were significantly associated with at least one clinical outcome endpoint: minimal residual disease (MRD) after induction I, event free survival (EFS), or overall survival (OS) in the two cohorts. In an independent cohort of patients from COG-AAML1031 trial (n=854), rs7265241 A>G remained significantly associated with EFS and OS. In multivariable analysis, adjusting for other prognostic factors such as race, age, risk group, and white blood cell count, all the SNPs remained independent predictors of clinical outcome endpoints. These results highlight the relevance of the SAMHD1 pharmacogenomics in context of response to Ara-C in AML and warrants the need for further validation in expanded patient cohorts.

show abstract

Section: Discussionmentioning

confidence: 99%

SAMHD1 single nucleotide polymorphisms impact outcome in children with newly diagnosed acute myeloid leukemia

Marrero

Cao

et al. 2023

Blood Advances

View full text Add to dashboard Cite

show abstract

“…Frontiers in Cell and Developmental Biology frontiersin.org myelogenous leukemia (AML) cells to cytarabine (Ara-C), as demonstrated by cell proliferation and Annexin V apoptosis assays (Zhang et al, 2022a). In colon cancer, Y-box binding protein 1 (YB-1) contributes to oxaliplatin resistance, and this resistance depends on NONO.…”

Section: Nonomentioning

confidence: 99%

“…Studies have shown that NONO prevents DCAF1-mediated SAMHD1 degradation, thereby increasing SAMHD1 stability. Silencing NONO was found to increase the sensitivity of acute myelogenous leukemia (AML) cells to cytarabine (Ara-C), as demonstrated by cell proliferation and Annexin V apoptosis assays ( Zhang et al, 2022a ). In colon cancer, Y-box binding protein 1 (YB-1) contributes to oxaliplatin resistance, and this resistance depends on NONO.…”

Section: Introductionmentioning

confidence: 99%

RNA binding proteins in cancer chemotherapeutic drug resistance

Vembuli,

Gor,

Ramalingam

et al. 2024

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Drug resistance has been a major obstacle in the quest for a cancer cure. Many chemotherapeutic treatments fail to overcome chemoresistance, resulting in tumor remission. The exact process that leads to drug resistance in many cancers has not been fully explored or understood. However, the discovery of RNA binding proteins (RBPs) has provided insight into various pathways and post-transcriptional gene modifications involved in drug tolerance. RBPs are evolutionarily conserved proteins, and their abnormal gene expression has been associated with cancer progression. Additionally, RBPs are aberrantly expressed in numerous neoplasms. RBPs have also been implicated in maintaining cancer stemness, epithelial-to-mesenchymal transition, and other processes. In this review, we aim to provide an overview of RBP-mediated mechanisms of drug resistance and their implications in cancer malignancy. We discuss in detail the role of major RBPs and their correlation with noncoding RNAs (ncRNAs) that are associated with the inhibition of chemosensitivity. Understanding and exploring the pathways of RBP-mediated chemoresistance will contribute to the development of improved cancer diagnosis and treatment strategies.

show abstract

“…The viral restriction factor SAMHD1 is also considered as an anticancer target. The protein is frequently upregulated in cytarabine (Ara-C)-resistant AML [ 90 ]. SAMHD1 inhibitors are being developed for the sensitization of leukemia cells to nucleoside analogue-based therapy [ 91 ].…”

Section: Cd81 Biology Trafficking and Signalingmentioning

confidence: 99%

Targeting of Tetraspanin CD81 with Monoclonal Antibodies and Small Molecules to Combat Cancers and Viral Diseases

Bailly

Thuru

2023

Cancers

View full text Add to dashboard Cite

Tetraspanin CD81 plays major roles in cell-cell interactions and the regulation of cellular trafficking. This cholesterol-embarking transmembrane protein is a co-receptor for several viruses, including HCV, HIV-1 and Chikungunya virus, which exploits the large extracellular loop EC2 for cell entry. CD81 is also an anticancer target implicated in cancer cell proliferation and mobility, and in tumor metastasis. CD81 signaling contributes to the development of solid tumors (notably colorectal, liver and gastric cancers) and has been implicated in the aggressivity of B-cell lymphomas. A variety of protein partners can interact with CD81, either to regulate attachment and uptake of viruses (HCV E2, claudin-1, IFIM1) or to contribute to tumor growth and dissemination (CD19, CD44, EWI-2). CD81-protein interactions can be modulated with molecules targeting the extracellular domain of CD81, investigated as antiviral and/or anticancer agents. Several monoclonal antibodies anti-CD81 have been developed, notably mAb 5A6 active against invasion and metastasis of triple-negative breast cancer cells. CD81-EC2 can also be targeted with natural products (trachelogenin and harzianoic acids A-B) and synthetic compounds (such as benzothiazole-quinoline derivatives). They are weak CD81 binders but offer templates for the design of new compounds targeting the open EC2 loop. There is no anti-CD81 compound in clinical development at present, but this structurally well-characterized tetraspanin warrants more substantial considerations as a drug target.

show abstract

Stabilization of SAMHD1 by NONO is crucial for Ara-C resistance in AML

Cited by 13 publications

References 46 publications

SAMHD1 single nucleotide polymorphisms impact outcome in children with newly diagnosed acute myeloid leukemia

SAMHD1 single nucleotide polymorphisms impact outcome in children with newly diagnosed acute myeloid leukemia

RNA binding proteins in cancer chemotherapeutic drug resistance

Targeting of Tetraspanin CD81 with Monoclonal Antibodies and Small Molecules to Combat Cancers and Viral Diseases

Contact Info

Product

Resources

About