2.5 Other B-cell lymphomas with CRISPR Cas9
Primary mediastinal B lymphoma (PMBL) is a tumor characterized by
genetic variants with a high degree of heterogeneity, the most common of
which is the XPO1 gene located in the chromosome 12p25.2 region. XPO1
point mutations are less frequent but are positively expressed in most
PMBL, and amplification of this gene is associated with poor prognosis
in patients with PMBL. Genomic abnormalities are also frequently present
in cHL, giving both a similar clinical presentation. The XPO1 gene
encodes export protein 1 (XPO1), which transports cargo proteins to the
nucleus by binding to cargo binding sites in the hydrophobic groove of
the cargo protein nuclear export region; it also prevents RNA
degradation by RNA polymerase II (Pol II) by reducing cargo protein
nuclear export and increasing the amount of cargo protein in the
nucleus. High heritability of E571K mutations in PMBL and cHL, but not
in other types of B lymphocytes. Hadjer Miloudi et al65 studied XPO1 E571K mutation in PMBL and cHL by
editing E571K gene using CRISPR-Cas9. XPO1 gene is expressed in each
solid and hematological tumors, whilst XPO1E571K gene is
spectrum-specific and is only observed in B cells66.
Every mRNA and protein contains XPO1 mutations, which primarily change
the subcellular localization of XPO1 and impact protein transport to the
cytoplasm, lysosomes, and mitochondria. On the cytoplasmic surface of
the nuclear envelope, XPO1 co-localizes with nucleoprotein 1, also known
as importin 1, KPNB1, or IPO1. Mutant XPO1 can attach to IPO1, which
alters the dynamics of associated cargo’s nuclear export and
import.2.6 Other B-cell lymphoma impact factors and CRISPR Cas9