Detection of LIM domain only 2 (LMO2) in normal human tissues and haematopoietic and non‐haematopoietic tumours using a newly developed rabbit monoclonal antibody

Abstract

2012) HistopathologyDetection of LIM domain only 2 (LMO2) in normal human tissues and haematopoietic and non-haematopoietic tumours using a newly developed rabbit monoclonal antibody Aims: We describe a new rabbit monoclonal antibody, raised against a fixation-resistant epitope of the transcription regulator LIM domain only 2 (LMO2). Methods and results: Lymphoma cell lines and a large series of normal and neoplastic samples were investigated by Western blot and immunohistochemistry. The antibody detected nuclear positivity for the protein, with the exception of a proportion of classical Hodgkin lymphomas (HLs), peripheral T cell lymphomas (PTCLs) and solid tumours that showed granular cytoplasmic staining. In normal lympho-haematopoietic tissues, LMO2 was expressed at different intensities by CD34 + blasts, haematopoietic precursors, germinal centre (GC), mantle and splenic marginal zone B cells. While reactive with only scattered elements in the thymus and nine of 237 PTCLs, the antibody stained 31 of 39 T-acute lymphoblastic lymphoma ⁄ leukaemias (T-ALLs) and the T-ALL-derived human leukaemic cell line, CCRF-CEM. LMO2 was found in 88% of B-acute lymphoblastic lymphoma ⁄ leukaemias (B-ALLs), 5% chronic lymphocytic leukaemias (CLLs) and 14%, 57% and 41% of mantle, follicular and Burkitt lymphomas, respectively. In the setting of diffuse large B cell lymphomas (DLBCLs), LMO2-positivity was related strongly to a GC phenotype. LMO2 was found in 83% primary mediastinal large B cell lymphomas (PMBLs) and 100% nodular lymphocyte predominant Hodgkin lymphomas (NLPHLs), whereas only 10% of classical HLs were stained. Acute and chronic myeloid leukaemias were usually positive. Conclusions: The new anti-LMO2 antibody can be applied confidently to routine sections, contributing to the differential diagnosis of several lymphoma subtypes, subtyping of DLBCLs and potential development of innovative therapies.

Protein Arginine Methyltransferase 5 (PRMT5) Inhibition Induces Lymphoma Cell Death through Reactivation of the Retinoblastoma Tumor Suppressor Pathway and Polycomb Repressor Complex 2 (PRC2) Silencing

“…Studies that examined expression of PRMT5, EZH2, and their associated epigenetic marks as well as RB1, phospho-RB1 (Ser-795), and RBL2 levels were performed on a second tissue microarray (TMA) generated from formalin-fixed, paraffin-embedded tissue samples corresponding to 16 MCL and 18 DLBCL cases, which were included in the original TMA studied for PRMT5 expression. The second TMA used in these experiments was constructed as reported previously (29). All cases were retrieved from the archives of the Hematopathology Unit, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna.…”

“…For negative controls, primary antibodies were omitted. A cutoff of staining of Ͼ30% of the examined cells was assigned as a positive score, according to formerly defined criteria (29). The staining intensity regarded as weak, moderate, or strong was also recorded.…”

“…However, because of limitation of tissue availability on most TMAs, these studies were performed on a newly constructed TMA as described previously (29). Both PRMT5 and its induced H3(Me 2 )R8 and H4(Me 2 )R3 marks were present in all cases of MCL, GCB-DLBCL, and ABC-DLBCL (Fig.…”

LMO2 attenuates tumor growth by targeting the Wnt signaling pathway in breast and colorectal cancer

“…Sporadic recent reports suggested that LMO2 is widely expressed in many other tissues, as well as some solid tumors. Furthermore, LMO2 was located specifically in the cytoplasm in some tissues, particularly in normal and malignant epithelial cells111213. However, the function of LMO2 in these tissues and tumors was rarely reported.…”

Pattern of MEF2B expression in lymphoid tissues and in malignant lymphomas

“…The high frequency of MEF2B expression in MCL might be taken as an indication of limited efficacy in distinguishing between MCL and FL. Expression of other currently used GC B cell markers, including CD10, BCL6, and LMO2, has also been found in MCL [31][32][33], which may further complicate the differential diagnosis of MCL. However, while expression of cyclin D1 establishes the diagnosis, heterogeneous MEF2B staining, as in the interfollicular compartment of FL, can still be a useful feature in the diagnosis of MCL.…”