[1344] BCL11b Gene Is Targeted by Structural and Numerical Chromosomal Aberrations in Mature T-Cell Lymphoma

E Haralambieva, E Leich, E Marques-Maggio, E Bachmann, A Zettl, A Rosenwald, HK Mueller-Hermelink, K Pulford. University of Wuerzburg, Wuerzburg, Germany; Viollier AG, Basel, Switzerland; Oxford University, Oxford, United Kingdom

Background: BCL11b is a transcriptional repressor, required for the differentiation and survival of α/β T lymphocytes and the development of the corticospinal motor neurons in the central nervous system. It is likely involved in cancergenesis either as a tumor-suppressor gene via inactivating mutations or deletions in murine irradiation induced lymphomas or as a transcriptional deregulator via recurrent chromosomal translocation in T-cell acute lymphoblastic leukemia. In this study we present data on BCL11b gene configuration and protein expression in series of mature T-cell lymphoma.
Design: 265 mature T-cell lymphoma, namely 119 peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS), 54 angioimmunoblastic T-cell lymphoma, 44 anaplastic large cell lymphoma, 13 extranodal T/NK lymphoma, 2 hepatosplenic T-cell lymphoma, 6 T-cell prolymphocytic leukaemia and 27 mycosis fungoides samples were selected from the files of the Institute of Pathology, Wuerzburg, Germany. All samples were classified according to the WHO classification criteria and studied for presence of genetic aberrations affecting BCL11b gene by newly designed interphase fluorescence in situ hybridization (FISH) assay in tissue microarray formate. BCL11b protein expression was tested by immunohistochemistry using rat monoclonal antibody 25B6 (Santa Cruz Biotechnology, Inc).
Results: Chromosomal breakpoint in the BCL11b genomic region was detected in 3(1%) out of 265 mature T-cell lymphoma samples. All cases were classified as PTCL, NOS and presented with lymphadenopathy and cutaneous infiltration in 2 male and 1 female adult patients, respectively. One of the samples carried concurrent breakpoint in TCR α/δ, suggesting a presence of an inv(14)(q11;q32), affecting the TCR α/δ and BCL11b loci. Genomic gain in BCL11b/14q32 was recognized in 84 (32%) samples, most frequently affecting PTCL, NOS. Varying level of BCL11b protein expression was observed in 67% of the samples, showing no correlation to the presence or absence of an underlying genetic aberration.
Conclusions: Our study identified BCL11b gene as a novel recurrent, though infrequent translocation partner in PTCL, NOS, affected also by numerical genetic aberrations. BCL11b protein is commonly expressed in mature T-cell lymphoma however it's biological and clinical significance remains unclear and merit further studies.
Category: Hematopathology

Tuesday, March 23, 2010 9:30 AM

Poster Session III # 199, Tuesday Morning


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