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.
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.
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).
Heterogeneity in the clinical course of MCL-indolent vs aggressive-is further delineated by a correlation with the mutational status of the variable region of immunoglobulin heavy chain, methylation status, and SOX-11 expression.
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.
We have measured MRD level in follow-up samples from 27 patients diagnosed with MCL using the molecular markers: t(11;14), IGH rearrangement and SOX11 expression.
We conducted immunohistochemical staining of C-MYC, Programmed cell death ligand 1 (PD-L1), CD8, Ki-67, p53 and SRY (sex determining region Y) -11 (SOX11) to investigate their expression in 64 patients with MCL.
In intravenous MCL xenograft models, SOX11<sup>+</sup> MCL cells display higher cell migration, invasion, and growth compared with SOX11-knockdown cells, and specific FAK and CXCR4 inhibitors impair SOX11-enhanced MCL engraftment in bone marrow.
To this end, since little data are available in the literature, four commercially available anti-SOX11 antibodies (two polyclonal and two monoclonal) were tested on 21 positive staging bone marrow (BM) biopsies from cyclin D1/SOX11-positive MCL patients (17 fixed in B5, 4 in 10% buffered formalin) and on 9 positive BM biopsies from leukemic non-nodal MCL patients.
An integrative epigenomic approach revealed 10,504 differentially methylated regions in regulatory elements marked by H3K27ac in MCL primary cases, including a distant enhancer showing de novo looping to the MCL oncogene SOX11.
However, recent data show that the neural transcription factor SOX11 is a disease defining antigen and several involved signaling pathways have been pin-pointed, among others the Wnt/β-catenin pathway that is of importance for proliferation in MCL.