Novel UHRF1-MYC Axis in Acute Lymphoblastic Leukemia

Park, Soyoung; Sater, Ali H. Abdel; Fahrmann, Johannes F.; Irajizad, Ehsan; Cai, Yining; Katayama, Hiroyuki; Vykoukal, Jody; Kobayashi, Makoto; Dennison, Jennifer B.; Mullighan, Charles G.; Gu, Zhaohui; Konopleva, Marina; Hanash, Samir M.

doi:10.3390/cancers14174262

Cited by 8 publications

(7 citation statements)

References 55 publications

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“…Proteomics analysis was performed as previously described [10, 11, 12, 13, 14]. For proteomic analysis of whole-cell extract (WCE), 2 × 10 7 cells were lysed in 1 mL of Tris-HCl (pH 8.0) containing 3% octyl-glucoside (1% w/v), 4M urea, and protease inhibitors (complete protease inhibitor cocktail, RocheDiagnostics), followed by sonication and centrifugation at 20,000g with collection of the supernatant, and filtration through a 0.22µm filter.…”

Section: Methodsmentioning

confidence: 99%

“…Total RNA extraction and qPCR was performed as previously described [13, 17]. Briefly, Total RNA was extracted using the RNeasy Mini Kit (Cat.…”

Section: Methodsmentioning

confidence: 99%

“…One fixed modification of carbamidomethyl at Cys (57.02146 Da) Propionamide at Cys (71.037114 Da) and variable modifications, oxidation at Met (15.9949 Da) and SILAC 13 C6 at Lys (6.0201 Da) were chosen. The purpose of adding SILAC 13 C6 was to filter out the possible Bovine proteins contaminated from the culturing media.…”

Section: Proteomics Analysismentioning

confidence: 99%

“…Total RNA extraction and qPCR was performed as previously described [13,17] and subsequently transferred to PVDF membranes using the Trans-Blot Turbo system (BioRad).…”

Section: Total Rna Extraction and Quantitative Pcr (Qpcr)mentioning

confidence: 99%

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EGFR inhibition in lung adenocarcinoma upregulates cell surface expression of the placental antigen ALPP and enhances efficacy of ALPP-ADC therapy

Chen

Hong

et al. 2023

Preprint

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Alkaline phosphatase placental type (ALPP) and ALPPL2 are closely related and regulated GPI anchored proteins that are known to be expressed on the cell surface in some cancers, whereas normal tissue expression is largely limited to the placenta. Clinical utility of ALPP is potentially limited by heterogenous expression in tumors. Here, we assessed ALPP and ALPPL2 surfaceome protein levels in 158 cancer cell lines and mRNA expression levels in 10,967 tumors representing 32 cancer types from The Cancer Genome Atlas (TCGA), which revealed ALPP, and to a lesser extent ALPPL2, to be variably expressed in several cancer types including lung adenocarcinoma (LUAD). Surface expression of ALPP was confirmed by tissue microarray analysis of 204 lung tumors. Using LUAD as a model system, we demonstrated that treatment with EGFR inhibitors, or induction of cancer cell quiescence via nutrient deprivation greatly enhanced ALPP surface expression. Mechanistic studies revealed that enhancement of surface ALPP expression in LUAD following gefitinib treatment was mediated through repression of EGFR signaling and activation of the transcription factor FoxO3a, which was identified as an upstream transcriptional regulator of ALPP. Using xenograft models of LUAD, we further demonstrated that gefitinib treatment upregulates surface expression of ALPP in LUAD cells but not in normal tissues. Combination therapy with gefitinib and an ALPP antibody conjugated with Monomethylauristatin F (ALPP-ADC-MAF) resulted in superior anti-cancer efficacy compared with gefitinib or ALPP-ADC-MAF alone. Our findings support a novel combination treatment modality that boosts the efficacy of ALPP-ADC directed therapy.

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Section: Methodsmentioning

confidence: 99%

“…Total RNA extraction and qPCR was performed as previously described [13, 17]. Briefly, Total RNA was extracted using the RNeasy Mini Kit (Cat.…”

Section: Methodsmentioning

confidence: 99%

Section: Proteomics Analysismentioning

confidence: 99%

“…Total RNA extraction and qPCR was performed as previously described [13,17] and subsequently transferred to PVDF membranes using the Trans-Blot Turbo system (BioRad).…”

Section: Total Rna Extraction and Quantitative Pcr (Qpcr)mentioning

confidence: 99%

See 2 more Smart Citations

EGFR inhibition in lung adenocarcinoma upregulates cell surface expression of the placental antigen ALPP and enhances efficacy of ALPP-ADC therapy

Chen

Hong

et al. 2023

Preprint

Self Cite

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“…Several genes from this group, such as UHRF1, MPZL1, CDK14, RACGAP1, RAB13, and others have oncogenic functions in various solid tumors, leukemias, and lymphomas either predicting poor prognosis, involved in tumor migration, metastasis, or maintenance [31][32][33][34][35] .…”

Section: Deregulated Promoter Methylation Is Associated With Changes ...mentioning

confidence: 99%

Genome-wide methylation profiling of Peripheral T-cell lymphomas identifies TRIP13 as a critical driver of tumor proliferation and survival

Nowialis,

Tobon,

Lopusna

et al. 2024

Preprint

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Cytosine methylation of genomic DNA contributes to the regulation of gene expression and is involved in normal development including hematopoiesis in mammals. It is catalyzed by the family of DNA methyltransferases (DNMTs) that include DNMT1, DNMT3A, and DNMT3B. Peripheral T-cell lymphomas (PTCLs) represent a diverse group of aggressive mature T-cell malignancies accounting for approximately 10–15% of non-Hodgkin lymphoma cases in the US. PTCLs exhibit a broad spectrum of clinical, histological, and immunophenotypic features with poor prognosis and inadequately understood molecular pathobiology. To better understand the molecular landscape and identify candidate genes involved in disease maintenance, we used high-resolution Whole Genome Bisulfite Sequencing (WGBS) and RNA-seq to profile DNA methylation and gene expression of PTCLs and normal T-cells. We found that the methylation patterns in PTCLs are deregulated and heterogeneous but share 767 hypo- and 567 hypermethylated differentially methylated regions (DMRs) along with 231 genes up- and 91 genes downregulated in all samples suggesting a potential association with tumor development. We further identified 39 hypomethylated promoters associated with increased gene expression in the majority of PTCLs. This putative oncogenic signature included the TRIP13 (thyroid hormone receptor interactor 13) gene whose both genetic and pharmacologic inactivation, inhibited cellular growth of PTCL cell lines by inducing G2-M arrest accompanied by apoptosis suggesting that such an approach might be beneficial in human lymphoma treatment. Altogether we show that human PTCLs are characterized by a large number of recurrent methylation alterations, and demonstrated that TRIP13 is critical for PTCL maintenance in vitro.

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Construction of a five-gene-based prognostic model for relapsed/refractory acute lymphoblastic leukemia

Zhou,

Min,

Liu

et al. 2024

Hematology

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Novel UHRF1-MYC Axis in Acute Lymphoblastic Leukemia

Cited by 8 publications

References 55 publications

EGFR inhibition in lung adenocarcinoma upregulates cell surface expression of the placental antigen ALPP and enhances efficacy of ALPP-ADC therapy

EGFR inhibition in lung adenocarcinoma upregulates cell surface expression of the placental antigen ALPP and enhances efficacy of ALPP-ADC therapy

Genome-wide methylation profiling of Peripheral T-cell lymphomas identifies TRIP13 as a critical driver of tumor proliferation and survival

Construction of a five-gene-based prognostic model for relapsed/refractory acute lymphoblastic leukemia

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