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Tumour-associated macrophages (TAMs) have been associated with survival in classic Hodgkin lymphoma (cHL) and other lymphoma types. The maturation and differentiation of tissue macrophages depends upon interactions between colony-stimulating factor 1 receptor (CSF1R) and its ligands. There remains, however, a lack of consistent information on CSF1R expression in TAMs. A new monoclonal antibody, FER216, was generated to investigate CSF1R protein distribution in formalin fixed tissue samples from 24 reactive lymphoid tissues and 187 different lymphoma types. We also analysed the distribution of CSF1R+, CD68+ and CD163+ macrophages by double immunostaining, and studied the relationship between CSF1R expression and survival in an independent series of 249 cHL patients. CSF1R+ TAMs were less frequent in B-cell lymphocytic leukaemia and lymphoblastic B-cell lymphoma than in diffuse large B-cell lymphoma, peripheral T-cell lymphoma, angioimmunoblastic T-cell lymphoma and cHL. HRS cells in cHL and, with the exception of three cases of anaplastic large cell lymphoma, the neoplastic cells in NHLs, lacked detectable CSF1R protein. A CSF1R+ enriched microenvironment in cHL was associated with shorter survival in an independent series of 249 cHL patients. CSF1R pathway activation was evident in the cHL and inactivation of this pathway could be a potential therapeutic target in cHL cases.

The OX-TES-4 antigen originally elicited an antibody response in 50% of diffuse large B-cell lymphoma (DLBCL) patients but not in control subjects. OX-TES-4 is encoded by a novel gene, MORC4, located at chromosome Xq22.3. The MORC4 protein contains a HATPase-c domain, CW zinc finger motif, nuclear localisation signals and a nuclear matrix-binding domain, together with a coiled-coil region. MORC4 mRNA is widely expressed at low levels in normal tissues, showing highest expression levels in placenta and testis. mRNA levels were increased in non-germinal centre-derived DLBCL and Hodgkin lymphoma cell lines, compared with germinal centre-derived DLBCL cell lines and normal B cells. Nineteen DLBCL patients (66%) expressed significantly higher levels of MORC4 mRNA than normal B cells ( P = 0·0031). The differential expression of MORC4 identifies this molecule as a potential lymphoma biomarker, whose overexpression may contribute to the immunological recognition of MORC4 by a subgroup of DLBCL patients. [ABSTRACT FROM AUTHOR]

Background: Chromosomal aberrations of BCL11A at 2p16.1 have been reported in a variety of B-cell malignancies and its deficiency in mice leads to a profound block in B-cell development. Results: Alternative pre-mRNA splicing of BCL11A produces multiple isoforms sharing a common N-terminus. The most abundant isoform we have identified in human lymphoid samples is BCL11AXL, the longest transcript produced at this locus, and here we report the conservation of this major isoform and its functional characterization. We show that BCL11A-XL is a DNA-sequence-specific transcriptional repressor that associates with itself and with other BCL11A isoforms, as well as with the BCL6 proto-oncogene. Western blot data for BCL11A-XL expression coupled with data previously published for BCL6 indicates that these genes are expressed abundantly in germinalcenter- derived B cells but that expression is extinguished upon terminal differentiation to the plasma cell stage. Although BCL11A-XL/BCL6 interaction can modulate BCL6 DNA binding in vitro, their heteromeric association does not alter the homomeric transcriptional properties of either on model reporter activity. BCL11A-XL partitions into the nuclear matrix and colocalizes with BCL6 in nuclear paraspeckles. Conclusion: We propose that the conserved N-terminus of BCL11A defines a superfamily of C2HC zinc-finger transcription factors involved in hematopoietic malignancies. [ABSTRACT FROM AUTHOR]