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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

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			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

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

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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).

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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

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

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AML PATIENTS WITH WILDTYPE TP53 AND DEFECTIVE TP53-MEDIATED APOPTOSIS HAVE A DISMAL SURVIVAL

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