In addition, compound 13e showed greater BTK selectivity and higher stability in human liver microsomes than IBN and potential safety improvement for the treatment of MCL.
The expression of SOX11 mRNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and the relationship of survival with SOX11 mRNA and MIPI in MCL patients was evaluated.
Accordingly, most MCL cell lines proved sensitive to the specific MCL-1 inhibitor S63845, and MCL-1 inhibition also proved efficacious in an MCL xenograft model.
Although <sup>18</sup> F-fluorodeoxyglucose positron emission tomography (<sup>18</sup> F-FDG PET) is commonly used for initial staging and therapeutic response evaluation in aggressive lymphomas, its prognostic utility for mantle cell lymphoma (MCL) is controversial.
Protein arginine methyltransferase-5 (PRMT5) is overexpressed in aggressive B-cell non-Hodgkin's lymphomas, including mantle cell lymphoma and diffuse large B-cell lymphoma, and supports constitutive expression of CYCLIN D1 and c-MYC.
Fatal hyperkalemia resulted from use of a recently recommended combination regimen for refractory/relapsed MCL in a phase 2 study, despite dose escalation and TLS prophylaxis suggesting increased risk of this regimen for patients with hyperleukocytosis.
Interestingly, our data revealed a potential inverse relationship between phosphorylated Y705 STAT3 and SOX11 expression in MCL cell lines, primary tumors, and patient-derived xenografts.
In summary, SOX11-negative MCL is characterized by more frequent leukemic non-nodal disease, classic morphology, more frequent expression of CD23 and CD200, and a lower Ki67 index.
Acalabrutinib is a novel second-generation oral Bruton tyrosine kinase inhibitor approved by the US Food and Drug Administration for relapsed MCL based on a clinical trial demonstrating an overall response rate of 81%.
The dysregulation of PI3K signaling has been implicated as an underlying mechanism associated with resistance to Bruton's tyrosine kinase inhibition by ibrutinib in both chronic lymphocytic leukemia and mantle cell lymphoma (MCL).
We performed genomic, metabolomic, and fluxomic analyses to evaluate the mechanism of action of the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib (IBR) in mantle cell lymphoma (MCL) cells.
SOX11-positive MCL showed a significant higher microvascular development than negative tumours (median MVA = 14.5 × 10<sup>-3</sup> versus 5.0 × 10<sup>-3</sup> P < 0.001; median MVD = 18.6/μm<sup>2</sup> versus 14.2/μm<sup>2</sup> , P = 0.021).
Clinically, the nonnodal MCL subset is notable for leukemic presentation, indolent behavior, and association with hypermutated IGHV and lack of SOX11 expression, which differentiates it from the conventional nodal MCL.
Clinically, the nonnodal MCL subset is notable for leukemic presentation, indolent behavior, and association with hypermutated IGHV and lack of SOX11 expression, which differentiates it from the conventional nodal MCL.