Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Histone deacetylase inhibition sensitizes TP53-mutated B-cell precursor acute lymphoblastic leukemia to chemotherapy

ABSTRACT: Histone deacetylase inhibition sensitizes TP53-mutated B-cell precursor acute lymphoblastic leukemia to chemotherapy

PROVIDER: PRJNA980094 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR24826700_1.fastq.gz	Fastqsanger.gz
	SRR24826700_2.fastq.gz	Fastqsanger.gz
	SRR24826701_1.fastq.gz	Fastqsanger.gz
	SRR24826701_2.fastq.gz	Fastqsanger.gz
	SRR24826702_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 90

Similar Datasets

Ataxia-telangiectasia mutated (Atm) disruption sensitizes spatially-directed H3.3K27M/TP53 diffuse midline gliomas to radiation therapy

Project description:Ataxia-telangiectasia mutated (Atm) disruption sensitizes spatially-directed H3.3K27M/TP53 diffuse midline gliomas to radiation therapy

| PRJNA1033668 | ENA

Histone deacetylase inhibition sensitizes TP53-mutated B-cell precursor acute lymphoblastic leukemia to chemotherapy

Project description:To determine how histone deacetylation inhibition synergizes with cytarabine, we performed RNA sequencing investigating which genes are affected in response to romidepsin, cytarabine or the combination

2024-01-10 | GSE234091 | GEO

Proteomic of anlotinib in TP53-mutated non-small cell lung cancer

Project description:Our study provides a profile of proteins and their related pathways in anlotinib-treated TP53-mutated NSCLC cells (H1299).

2024-09-25 | PXD056214 |

The XPO7-NPAT axis represents key vulnerabilities in TP53-mutated acute myeloid leukemia (scRNA-Seq)

Project description:Mutation of TP53, a tumor suppressor in cancer, is common and leads to extremely poor prognosis. To identify vulnerabilities in TP53-mutated tumors, we performed genome-wide CRISPR/Cas9 screens using isogenic Trp53 wild-type and knockout mouse acute myeloid leukemia (AML) lines. Here, we show that histone gene regulation governed by the XPO7-NPAT pathway is essential for survival of TP53-mutated AML cells. In TP53 wild-type cells, XPO7 enhances p53 nuclear localization and functions as a tumor suppressor, but in TP53-mutated cells, XPO7 promotes cell proliferation by retaining NPAT, a histone gene activator, in the nucleus. NPAT depletion led to genome-wide histone loss, enhancing vulnerability to genotoxic stress. Human AML cases show predominant expression of XPO7 and NPAT when TP53 is mutated, suggesting a potential therapeutic vulnerability.

2026-02-09 | GSE264596 | GEO

The XPO7-NPAT axis represents key vulnerabilities in TP53-mutated acute myeloid leukemia (RNA-Seq)

2026-04-22 | GSE264595 | GEO

The XPO7-NPAT axis represents key vulnerabilities in TP53-mutated acute myeloid leukemia (ATAC-Seq)

2026-04-22 | GSE264594 | GEO

Efficacy of melflufen in relapsed and refractory multiple myeloma patients with mutated or deleted TP53

Project description:Despite the development of several new treatments for multiple myeloma (MM) clinical challenges remain for patients with relapsed/refractory disease. This is especially so for the high-risk subgroup of patients with del(17p) who have poor response and significantly shorter survival compared to patients without this aberration. Here, we report the clinical efficacy of melphalan flufenamide (melflufen) in patients with del(17p) from the OCEAN randomized, open label, head-to-head, phase III clinical trial. In the del(17p) subgroup, melflufen plus dexamethasone treatment resulted in favorable progression free survival compared to the pomalidomide plus dexamethasone arm. To understand the superior efficacy of melflufen in TP53 mutated MM, we compared drug response between melflufen and melphalan in primary MM cells from patients with del(17p)/TP53 mutated disease. In line with the clinical data ex vivo sensitivity to melfufen was independent of the TP53 mutation status. To better understand the mechanism of action of melflufen, we investigated DNA damage, apoptosis kinetics and mitochondrial function in TP53 wild type and double mutant (TP53-/-) myeloma cells after treatment with melflufen, melphalan or cyclophosphamide. Melflufen demonstrated superior in vitro efficacy in comparison to the other two alkylators. Comparison of gene expression profiles and DNA damage pathway alterations upon drug treatment in the TP53 wild type and double mutant MM cell lines revealed qualitative differences between melflufen and melphalan. Our insights into the molecular mechanisms of melflufen activity in mutant TP53 genetic background support its clinical efficacy and application in the del(17p) and mutant TP53 MM patient population.

2025-12-31 | GSE254959 | GEO

Immune recovery in tumor microenvironment of TP53-mutated AML following venetoclax combination therapy

Project description:The BCL-2 inhibitor venetoclax combined with the hypomethylating agent azacitidine or with low-dose cytarabine significantly improves response rates and overall survival (OS) for newly diagnosed unfit and relapsed / refractory (R/R) acute myeloid leukemia (AML) patients. We retrospectively analyzed our experience with venetoclax combination therapy in 41 unfit AML patients (23 untreated, 18 R/R). Overall response rates were 78.3% for untreated patients and 61.1% for R/R patients. TP53 alterations were observed in 13 patients (31.7%) and were identified as an independent predictor of poor outcome (p=0.0008). We further conducted single-cell RNA sequencing in bone marrow, sampled before and after venetoclax and azacitidine treatment, of three TP53-mutated AML patients who achieved complete remission (CR) or CR with incomplete hematologic recovery. After treatment, numbers of cells expressing anti-apoptotic genes such as BCL2 and MCL1 decreased. CD4 T cells, cytotoxic CD8 T cells, and NK cells significantly increased both in number and in levels of gene expression associated with cytotoxicity post-treatment, confirming immune recovery in the tumor microenvironment. Residual AML cells expressed CD47 and CLEC12A (CLL1). These results indicate that venetoclax combination therapy of AML is promising in real-world clinical practice and suggest a role for ancillary treatment targeting antigens expressed on residual AML cells as a therapeutic strategy in TP53-mutated AML.

2025-08-30 | GSE306339 | GEO

Compare proB cells from WT, Tp53-/-, Lnk-/-, Tp53-/-Lnk-/- mice and Tp53-/-Lnk-/-B-ALL

Project description:The adaptor protein LNK (SH2B3) has emerged as an important protein in regulating B cell development B cell leukemia. Loss-of-function mutations in LNK (SH2B3) are found in Philadelphia chromosomeâlike acute lymphoblastic leukemia (Ph-like ALL), but how LNK regulates normal B cell development or promotes leukemogenesis remains unclear. We found that combined loss of Lnk and tumor suppressors Tp53 in mice triggers a highly aggressive and transplantable precursor B-ALL. This study aims to investigate the molecular mechanism by which LNK regulates B-ALL development. We performed expression profiling of bone marrow proB progenitors from WT, Tp53-/-, Lnk-/- and preleukemic healthy Tp53/Lnk double knockout (DKO) mice, as well as leukemic bone marrow cells from DKO mice that have developed B-ALL. Results suggest that Tp53-/-Lnk-/- B-ALLs display similar gene expression profiles to human Ph-like B-ALLs, suggesting this model for preclinical and molecular studies. B220+CD19+CD43+AA4.1+IgM-NK1.1-Ly6c- bone marrow proB cells were double sorted from WT, Tp53-/-, Lnk-/- and preleukemic healthy Tp53/Lnk double knockout (DKO) mice, as well as leukemic bone marrow cells from DKO mice that have developed B-ALL. RNA was isolated using miRNeasy kit from QIAGEN and processed using the NuGEN Pico kit. The microarray analysis was performed at the PENN Molecular Profiling/Genomics Facility using GeneChip Mouse Gene 2.0ST array (Affymetrix).

2016-04-01 | E-GEOD-76940 | biostudies-arrayexpress

Immune recovery in tumor microenvironment of TP53-mutated AML following venetoclax combination therapy

Project description:Immune recovery in tumor microenvironment of TP53-mutated AML following venetoclax combination therapy

| PRJNA1310505 | ENA