Identification of uniquely expressed transcription factors in highly purified B‐cell lymphoma samples

Abstract

Transcription factors (TFs) are critical for B-cell differentiation, affecting gene expression both by repression and transcriptional activation. Still, this information is not used for classification of B-cell lymphomas (BCLs). Traditionally, BCLs are diagnosed based on a phenotypic resemblance to normal B-cells; assessed by immunohistochemistry or flow cytometry, by using a handful of phenotypic markers. In the last decade, diagnostic and prognostic evaluation has been facilitated by global gene expression profiling (GEP), providing a new powerful means for the classification, prediction of survival, and response to treatment of lymphomas. However, most GEP studies have typically been performed on whole tissue samples, containing varying degrees of tumor cell content, which results in uncertainties in data analysis. In this study, global GEP analyses were performed on highly purified, flow-cytometry sorted tumor-cells from eight subgroups of BCLs. This enabled identification of TFs that can be uniquely associated to the tumor cells of chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), hairy cell leukemia (HCL), and mantle cell lymphoma (MCL). The identified transcription factors influence both the global and specific gene expression of the BCLs and have possible implications for diagnosis and treatment. Am. J. Hematol. 85:418-425, 2010. V

Cellular origin and pathophysiology of chronic lymphocytic leukemia

“…2 g). Similar results were obtained by applying a list of 19 transcription factors with specific expression in CLL, but not in diffuse large B cell lymphoma, hairy cell leukemia, mantle cell lymphoma or follicular lymphoma (Andréasson et al, 2010;unpublished data). This further argues for a close relationship of normal CD5 + B cells and CLL, as CLL-specific genes include typical CD5 + B cell genes.…”

MicroRNA profiling of follicular lymphoma identifies microRNAs related to cell proliferation and tumor response

“…4 Additional molecular lesions or secondary hits are required to cooperate with BCL2 in the evolution of the malignant phenotype, although the precise mechanisms of lymphomagenesis remain to be elucidated. Gene expression profile studies of FL further suggest that the lymph node microenvironment may play a role in the biology of FL through tumor infiltrating T cells and macrophages, [5][6][7][8][9] possibly involving cytokines 10,11 or other immunomodulatory mechanisms.…”

Dysregulation of autophagy in human follicular lymphoma is independent of overexpression of BCL-2

“…DLBCL and reactive B-cells were identified by CD20 expression while FL B-cells were isolated based on dual expression of CD19 and CD10. FL B-cells were further confirmed as the malignant cell population by demonstrating kappa/lambda (κ/λ) light chain restriction [ 47 ].…”