ML, et al. Mutations in the genes coding for the NF-{kappa}B regulating factors IκBα and A20 are uncommon in nodular lymphocyte-predominant Hodgkin lymphoma. Haematologica. 2010; 95(1) 1 TFH cells are characterized by their homing capacity in CXCL13-rich areas, such as B-cell follicles, through CXCR5 expression and their ability to support immunoglobulin production. The differentiation and homing of TFH, as well as their interactions with B cells, have been the subject of intense research and several markers have been identified as components of the TFH signature. Thanks to gene expression profiling carried out on peripheral T-cell lymphomas, a TFH signature has been reported in angioimmunoblastic T-cell lymphoma (AITL) and in follicular T-cell lymphoma.2-4 Several markers that identify TFH cells are now used in hematopathology to reinforce the diagnostic criteria of AITL. In this issue of the Journal, Marafioti et al.5 describe that inducible T-cell co-stimulatory molecule (ICOS), a CD28 homolog implicated in the regulation of T-cell differentiation and function, appears to be a relevant marker for the diagnosis of TFH-derived lymphoma such as AITL and follicular T-cell lymphoma. This review first summarizes the recent evidence on TFH cell differentiation and the present state of knowledge on molecules expressed by TFH cells. Then, from this perspective, the potential implications of TFH cells in lymphomagenesis and as part of the tumor microenvironment are covered. Lineage and differentiation of follicular T-helper cellsTH cell responses are heterogeneous and effector function choice is imposed during initial activation of the naïve TH cells through the expression of transcription factors. It is now clear that TFH cells belong to a subset of TH cells that differ from the other TH cell subsets. Indeed, TH1 cells express STAT4, STAT1 and T-box transcription factor/Tbet, TH2 cells express GATA3, TH17 cells express retinoid related orphan receptor (RORγt) and regulatory T cells (Treg) express FOXP3. It has recently been shown that the TFH cell differentiation program is controlled by BCL6. 6,7 TFH cells upregulate BCL6 which in turn blocks TH1, TH2 and TH17 cell differentiation by repressing their selective transcription factors. 6 Moreover, BCL6 antagonizes the expression of Blimp-1 transcription factor, which is preferentially expressed by TH cells in the T zone area. 6,8 BCL6 also represses the expression of miR-17-92, a micro RNA that down-regulates CXCR5 expression, which is essential for TFH cell function. Finally over-expression of BCL6 in activated TH cells induces expression of interleukin (IL)-6 receptor and IL-21 receptor, which are both required for TFH cell generation as shown by the role of IL-6 and IL-21 in TFH cell differentiation.9 ICOS is also implicated in the regulation of TFH cell differentiation. Once engaged with its ligand (ICOS-L), expressed on antigen-presenting cells including B cells, ICOS induces the production of helper cytokines such as IL-2, IL-4 and especially IL-10 and IL-21.10 I...

Hepatic veno-occlusive disease (VOD) is a major regimen-related toxicity after bone marrow transplantation (BMT). Endothelial injury, leading to deposition of coagulation factors within the terminal hepatic venules, is believed to be the key event in the pathogenesis of VOD. To evaluate the benefit and the safety of a VOD prophylaxis with anticoagulants, we conducted a prospective randomized trial of continuous infusion of low-dose heparin among 161 patients under-going either allogeneic (n = 79) or autologous BMT (n = 81). Patients were randomized to receive (n = 81) or not receive (n = 80) prophylactic heparin 100 U/kg/d by continuous infusion from day -8 until day +30 post-BMT. Heparin was found to be highly effective in preventing VOD, which occurred in 11 of 80 patients (13.7%) in the control group versus 2 of 81 (2.5%) in the heparin group (P less than .01). Furthermore, none of the 39 patients in the heparin group developed VOD after allogeneic BMT, versus 7 of 38 (18.4%) in the control group (P less than .01). This prophylactic effect was achieved without added risk of bleeding. Indeed, the low-dose heparin we used did not prolong the partial thromboplastin time and did not increase the red blood cell and platelet requirements. It is therefore recommended that heparin prophylaxis be part of early mortality prevention programs after BMT.

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The cytotoxic T-cell and natural killer (NK)-cell lymphomas and related disorders are important but relatively rare lymphoid neoplasms that frequently are a challenge for practicing pathologists. This selective review, based on a meeting of the International Lymphoma Study Group, briefly reviews T-cell and NK-cell development and addresses questions related to the importance of precise cell lineage (αβ-type T cell, γδ T cell, or NK cell), the implications of Epstein-Barr virus infection, the significance of anatomic location including nodal disease, and the question of further categorization of enteropathy-associated T-cell lymphomas. Finally, developments subsequent to the 2008 World Health Organization Classification, including the recognition of indolent NK-cell and T-cell disorders of the gastrointestinal tract are presented.