Our novel finding of specific overexpression of Sox11 mRNA and nuclear protein in both cyclin D1-positive and - negative MCL may be useful for the diagnosis of MCL as a complement to cyclin D1 and also suggests a functional role for Sox11 in MCL.
SOX11 nuclear protein was detected in 50 cases (93%) of conventional mantle cell lymphoma and also in the 12 cyclin D1-negative cases of mantle cell lymphoma, the six cases of lymphoblastic lymphomas, in two of eight cases of Burkitt's lymphoma, and in two of three T-prolymphocytic leukemias but was negative in the remaining lymphoid neoplasms.
We surveyed lymphomas to determine the range of expression of the mantle cell lymphoma-associated SOX11 transcription factor and its relation to cyclin D1.
In conclusion, we defined nonnodal presentation, predominantly hypermutated IGVH, lack of genomic complexity, and absence of SOX11 expression as qualities of a specific subtype of iMCL with excellent outcomes that might be managed more conservatively than cMCL.
Data showed the transcriptional levels of SOX11 and cyclin D1 were higher for the mantle cell lymphoma (MCL) samples compared with chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), hairy cell leukemia (HCL), splenic marginal zone lymphoma (SMZL), and healthy collators.
The novel monoclonal SOX11-specific antibody offers high sensitivity and improved specificity in IHC-P based detection of MCL and its expanded use in flow cytometry analysis of blood and tissue samples may allow a convenient approach to early diagnosis and follow-up of MCL patients.
The global genomic profile and the high complexity of the 32 cyclin D1(-) SOX11(+) MCL patients analyzed by copy number arrays were similar to the conventional cyclin D1/SOX11MCL.
Our results suggest that SOX11 contributes to tumor development by altering the terminal B-cell differentiation program of MCL and provide perspectives that may have clinical implications in the diagnosis and design of new therapeutic strategies.
In this issue of Blood, Salaverria et al report that more than half of Cyclin D1- (CCND1) negative SOX11-positive mantle cell lymphoma (MCL) had CCND2 gene rearrangement predominantly with immunoglobulin (IG) light chain genes.(1)
Robust consensus clustering defined 2 main MCL subgroups with significant differences in the immunoglobulin (IGHV) mutational status, SOX11 expression, genomic complexity, and nodal clinical presentation.
In such cases, the transcription factor SOX11 represents an important diagnostic marker, as it is expressed in most MCLs and, in particular, in all cyclin D1-negative MCLs reported so far.
Our findings suggest that high SOX11 expression is associated with improved survival in a subset of MCL patients, particularly those treated with intensive chemotherapy.
To the best of our knowledge this is the first report stating that quantification of SOX11 can be used as an minimal residual disease marker equal to the key translocation t(11;14) in MCL.
We suggest that implementing detection of SOX11 in diagnostic flow cytometry would be beneficial for accurate and reliable diagnosis of MCL, especially for distinguishing cases of MCL and B-CLL/SLL with aberrant immune phenotypes, and for cases of rare cyclin D1 negative MCL.