The subcellular Sox11 distribution pattern identifies subsets of mantle cell lymphoma: correlation to overall survival

Abstract

SummaryGene expression analysis demonstrated high expression of the neuronal transcription factor SOX11 in mantle cell lymphoma (MCL). In contrast to follicular lymphoma, small lymphocytic lymphoma and reactive lymphoid tissue, most MCLs tested (48/53 patients) expressed sox11 protein in the nucleus. Therefore nuclear sox11 expression represents a new tumour marker for a subset of MCL. However, 5/53 MCL cases expressed sox11 only in the cytoplasm; these MCL patients had a shorter survival compared to MCL with nuclear sox11 expression. These results suggest sox11 expression as a new diagnostic marker in MCL that could be related to the clinical and biological behaviour of MCL.Keywords: mantle cell lymphoma, sox11, nuclear expression, survival, proliferation.short report Materials and methods Tissue and cell linesTumour samples comprised MCL (n = 53), SLL (n = 5) and FL (n = 7) diagnosed at the Department of Pathology, Karolinska University Hospital, Stockholm, Sweden. All diagnoses were established by morphology, immunophenotyping by flow cytometry, immunohistochemistry for cyclin D1 and fluorescence in situ hybridization analysis for the (11;14)(q13;q32). Control tissues were from tonsil tissue (n = 1) and reactive lymph nodes (n = 4). Frozen tissue was stored and handled as described in . Cell linesThe MCL cell lines Rec1, Granta519 and JeKo, the plasma cell leukaemia cell line SK-MM-2, the mouse pituitary cell line AtT20 cell line transfected with cDNA for the rat CB1 receptor and the wild type AtT20 cell line, the acute T-cell leukaemia cell line Jurkat, the precursor T-cell leukaemia cell line MOLT-4 and the breast cancer cell line MCF7 were cultured as previously described (Islam et al, 2003;Flygare et al, 2005;Gustafsson et al, 2006). Gene expression analysisLymph node (n = 10), spleen (n = 3), tonsil (n = 2) and a biopsy from tongue base (n = 1) from 16 patients with MCL were investigated and compared to reactive lymph nodes (n = 6). The methodology and part of this data has been previously published . The data was analysed using Affymetrix Micro array Suite version 5AE0 (Affymetrix, Inc., Santa Clara, CA, USA). Each of the MCL was compared to each of the reactive lymphoid samples. Comparative analyses were carried out on the expression data using Affymetrix Datamining Tool version 3AE0.cDNA synthesis and reverse transcription polymerase chain reaction (RT-PCR) for SOX11Two micrograms of total RNA from primary MCL, FL, reactive lymph nodes, cell lines, mouse 7-d embryo (BD Biosciences Clontech, Palo Alto, CA, USA) and human fetal brain (BD Biosciences) was used for cDNA synthesis using First-strand cDNA synthesis kit (Amersham Biosciences AB, Uppsala, Sweden) according to the manufacturer's protocol. The primers used for RT-PCR were according to Lee et al (2002). For SOX11, 2 ll cDNA was amplified in a volume of 20 ll containing 0AE5 lmol/l of each primer, 100 lmol/l of each dNTP, 15 mmol/l Tris-HCl (pH 8AE0), 50 mmol/l KCl, 1AE5 mmol/l MgCl 2 and 1 Unit Taq Gold Polymerase (Applied Biosystems, Foster Ci...

Indolent mantle cell leukemia: a clinicopathological variant characterized by isolated lymphocytosis, interstitial bone marrow involvement, kappa light chain restriction, and good prognosis

“…23 Wang and colleagues demonstrated shorter survival in 5/53 patients with SOX11 cytoplasmic protein expression compared to 48/53 with SOX11 nuclear protein expression. 24 Consistent with other reports that stated that 78-93% of cases are positive, we found that the great majority (91%) of nodal MCL cases express SOX11; however, in our cohort of indolent leukemic MCL cases only one of five showed low-level positivity. 9,11,21,25 This was statistically different from typical nodal MCL.…”

“…7,9 The pattern has not been well characterized but appears to have no prognostic relevance. 24 Bone marrow findings have not been described in the type of patients with leukemic, non-nodal disease who are presented here. We show that there is uniformly low tumor burden in the marrow with sparsely distributed interstitial single cyclin D1 + lymphocytes or, uncommonly, subtle interstitial aggregates, representing less than 5% of cellularity.…”

Nuclear expression of sox11 is highly associated with mantle cell lymphoma but is independent of t(11;14)(q13;q32) in non-mantle cell B-cell neoplasms

“…These patients had shorter survival compared with mantle cell lymphomas with nuclear sox11 staining. 7 Ek et al evaluated sox11 expression in 18 whole tissue sections of mantle cell lymphomas, including 16 classical and 2 blastoid mantle cell lymphomas. One case was negative for nuclear sox11 staining, and this case was a blastoid variant.…”

“…[3][4][5] Recently, sox11, a transcription factor involved in embryonic neurogenesis and tissue remodeling, has been found to be expressed in the nuclei of mantle cell lymphoma cells. 6,7 This intriguing finding raises the question about the possible association between the nuclear expression of sox11 and t(11;14)(q13;q32). 6 The SRY (sex-determining region Y)-box11 (SOX11) gene is mapped to chromosome 2p25 and belongs to the SRY-related high mobility group (HMG) box (SOX) gene family characterized by containing the HMG domain with high identity to the HMG domain in SRY.…”

Strong lymphoid nuclear expression of SOX11 transcription factor defines lymphoblastic neoplasms, mantle cell lymphoma and Burkitt's lymphoma

“…2 Common MCL simulators do not express nuclear SOX11 but questions remain as to its relation to cyclin D1 (CCND1) and whether SOX11 is restricted to MCL. We surveyed most categories of B-and T-cell lymphomas for SOX11, including plasmacytoma/myeloma 3 and hairy cell leukemia, which are characterized by elevated levels of CCND1.…”