Blood: Activated AKT triggers CLL by overactivated Notch1→ Richter conversion

Richter syndrome is a rare type of lymphatic hemagtic system syndrome.
From one cell type of leukemia to or in combination with another type of cellular lymphoma, the classic Richter's syndrome;
(RT) is an invasive lymphoma that occurs in chronic lymphocytic leukemia (CLL).
conversion was associated with CLL phase gene abnormalities involving TP53, CDKN2A, MYC, and NOTCH1, however, a significant proportion of RT cases lacked CLL-related events.
AKT activation enhancement was associated with an increase in CLL→RT conversion in the study, the researchers found higher levels of AKT phosphorylation in patients with high-risk CLL and RT patients with TP53 and NOTCH1 mutations.
in mice with E-TCL1 Akt compositional activation induced DLBCL esoteric in the E-TCL1 CLL mouse model, overactivation of the Akt gene led to the conversion of CLL to RT, significantly reducing survival and invasive lymphoma esoteric.
in the absence of relapsed mutations, the researchers identified a genome mutation map between CLL and DLBCL.
Notch1 activation promotes RT's multi-histological analysis of phosphatized proteomics/proteomics and single-cell transcriptional maps in Akt-induced mice RT, and it is found that the highly invasive lymphoma cell subgroup developed by CLL cells can be defined by the S100 protein and activated by the Notch ligation expressed by T cells.
the same way that notch1, which is active, can induce mouse CRLs to be converted to RT.
, by inducing the Notch signal between RT cells and micro-environmental T cells, the study confirmed that Akt activation is the initiation event of the conversion of CLL to invasive lymphoma.