Detection of LMO2 in Normal Human Tissues and Haematopoietic and Non-Haematopoietic Tumours by a Newly Developed Rabbit Monoclonal Antibody.

LMO2 is a transcription factor with a central role in haematopoietic development and angiogenesis. High levels of LMO2 transcript were reported in CD34⁺ stem cells and strong protein expression was observed in endothelia, germinal centre B cells (GCB) and some B cell lymphomas. Activation of LMO2 has been demonstrated in T-ALL as a consequence of translocations or deletions and its expression in diffuse large B-cell lymphomas is associated with favourable outcome. Furthermore, correlation between LMO2 expression and tumour progression has been reported in prostatic carcinoma.

The expression pattern of a newly developed rabbit monoclonal antibody raised against a fixation-resistant epitope of the LMO2 protein was studied in human normal and pathologic samples.

Normal haematopoietic and non-haematopoietic tissue sections, tissue micro-arrays including 1452 neoplastic samples, 11 lymphoma-derived cell lines and CD34⁺/CD38⁻ stem cells, purified from human umbilical cord blood, were investigated by single and double immunostaining.

Strong LMO2 expression was found in CD34⁺/CD38⁻ stem cells and in contrast to previous studies, the anti-LMO2 rabbit monoclonal distinctively labelled normal mantle, monocytoid and splenic marginal zone B cells. A few LMO2⁺/CD34⁺ cells were detected in the thymic cortex, most likely representing T cell precursors. Tables 1 and 2 summarise the results obtained in tumours and lymphoma-derived cell lines. Among B cell neoplasms, LMO2 was highly expressed in B-lymphoblastic lymphoma/leukaemia (87%) and heterogeneously in MCL (14%), FL (57%) and BL (37%). In DLBCL, LMO2 positivity was closely related to those cases with a “germinal centre” phenotype. LMO2 nuclear positivity was observed in all cases of LPHL; interestingly Reed-Sternberg cells in CHL showed LMO2 cytoplasmic staining in 10% of cases. The constant expression in T-ALL highlights the pathogenetic role and diagnostic significance of LMO2 in this setting as opposed to PTCLs (usually negative). Detection of LMO2 was observed in the majority of AML and CML cases investigated. Different types of carcinoma expressed LMO2 that was found to be mainly cytoplasmic.

The newly developed anti-LMO2 rabbit monoclonal antibody represents a powerful reagent for detection of LMO2 protein in routine samples as compared to the previously published monoclonal anti-LMO2. Its frequent expression among haematological malignancies (e.g. T-ALL, B-ALL and AML) indicates LMO2 as putative therapeutic target as evidenced by RNA-silencing studies in experimental models.

No relevant conflicts of interest to declare.