Accession |
PRJNA309083 |
Title |
Compare proB cells from WT, Tp53-/-, Lnk-/-, Tp53-/-Lnk-/- mice and Tp53-/-Lnk-/-B-ALL |
Relevance |
ModelOrganism |
Data types |
Transcriptome or Gene expression |
Sample scope |
Multiisolate |
Organism |
Mus musculus [Taxonomy ID: 10090]
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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 chromosome–like 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.
Overall design: 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). |
Publication |
PubMed ID |
Article title |
Journal name |
DOI |
Year |
26974155
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External link |
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Organization |
Tong, Pediatrics, Children's Hospital of Philadelphia, and University of Pennsylvania School of Medicine |
Data Source |
NCBI |