2.2.1 BCL6 gene
DLBCL originates in the germinal
center (GC) stage of B-cell differentiation 31, and
BCL6, a core transcription factor of the GC response, has been shown to
be an oncogene that can develop into lymphoma.
Rebecca Caeser et al32 used steady Cas9 reverse transcription in primary,
human GC B cells and proven that the machine can be used for gRNA
targeted targeting. In CRISPR Cas9 screen TP53, GNA13, CDKN2A, ATRX,
NFKBIA, ZFP36L1, ZNF281, PTEN, FBXO11, FUBP1, S1PR2 and NFKBIE have been
strongly enriched and most elements suppressed lymphoma, whilst tumor
cell proliferation used to be enhanced with the aid of TSG inactivation.
The histone modifiers CREBBP, EP300 and KMT2D are lacking in the CRISPR
screen, and these genes exhibit very frequent inactivating mutations in
DLBCL and follicular lymphoma 33,34. The most striking
discovering in this study was once the efficient enrichment of gRNAs
targeting GNA13 and its upstream receptors S1PR2 and P2RY8.GNA13 is
typically viewed an oncogene and its inactivating mutations are frequent
in lymphomas however uncommon in different varieties of malignancies, so
its enrichment in the display reinforces the specificity of this system
for the pathogenesis of GC lymphomas.