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