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Non-Hodgkin Lymphoma
Published in Tariq I. Mughal, Precision Haematological Cancer Medicine, 2018
Most men with PTL, a unique extranodal lymphoma, fare well with R-CHOP, with >95% achieving complete remission, but the risk of relapse, in particular CNS and contralateral testis, remains high and continuous. For these reasons, CNS prophylaxis with intrathecal chemotherapy, usually methotrexate and contralateral testicular RT, is administered to patients on achieving complete remission with R-CHOP. The presence of FOXP1 and TCL1 genes have been proposed as candidate poor-risk biomarkers. Novel treatment approaches for relapse and refractory PTL (including BTK inhibitors, such as ibrutinib), immunomodulatory agents (for example lenalidomide) and immune checkpoint inhibitors (such as nivolumab) have demonstrated promising results in small studies and further investigations are ongoing.
Diffuse Large B-Cell Lymphoma and its Variants
Published in Wojciech Gorczyca, Atlas of Differential Diagnosis in Neoplastic Hematopathology, 2014
FOXP1 expression has been demonstrated in a subset of DLBCLs and is more common in the non-GCB, ABC type. Uniform high FOXP1 expression was demonstrated in ~18% patients with DLBCL. The high level of expression was almost exclusively confined to patients who lacked the GCB phenotype, who expressed MUM1 and BCL2 in the absence of t(14;18), and who were identified as a subgroup of patients with particularly poor outcome in a group with already poor prognosis. Positive FOXP1 expression is an independent poor prognostic factor in DLBCL [57,58]. T-cell leukemia/lymphoma-1A (TCL1A) mRNA overexpression in DNA microarray and tissue microarray analysis was shown to correlate with the relapse rate in DLBCL patients [59]. Table 13.2 shows molecular, pathogenetic, and clinical features distinguishing GCB-like and ABC-like DLBCLs.
Pathobiology and molecular basis of MALT lymphoma
Published in Franco Cavalli, Harald Stein, Emanuele Zucca, Extranodal Lymphomas, 2008
Francesco Bertoni, Randy D Gascoyne
The t(3;14)(p14;q32) is the most recently described translocation and results in the juxtaposition of the transcription factor FOXP1 located on chromosome 3p14 next to the enhancer region of the IGH genes.6 The pathogenetic relevance of this translocation is still unclear. FOXP1 is normally expressed by a fraction of mantle zone B cells and of germinal center and pregerminal center B cells42 and it is necessary for the transition from pro-B cell to pre-B cell.43 Strong nuclear expression of FOXP1 is associated with a poor clinical outcome and appears associated with an elevated risk of transformation to diffuse large B-cell lymphoma (DLBCL).44 Indeed, FOXP1 expression and translocations or gains/amplification of FOXP1 locus determine a poor prognosis in de-novo DLBCL.45–47
Regulatory T cells as therapeutic targets and mediators
Published in International Reviews of Immunology, 2019
By appropriate treatment (Costimulation, TCR activation, TGFβ and IL-2), conventional naïve T cells can be converted to induced Tregs (iTregs) in vitro (Figure 1B). This protocol enables us to use naïve T cells from peripheral blood to manufacture iTregs for ACT as natural Tregs are comparatively rare. However, iTregs are known to be plastic [55] and under an inflammatory host environment, can convert to effector T cells and worsen the disease. Therefore, it is imperative to understand the molecular mechanisms which underlie such transmutations in iTreg phenotypes. Pharmacological agents which stabilize expression of FOXP3 in iTregs may positively affect Treg mediated ACT. Recently, we have reported that sister transcription factor of Foxp3, Foxp1 [56] is essential for maintenance of Foxp3 expression in mouse iTregs. A loss of Foxp1 leads to gradual loss of Foxp3 and results in intestinal inflammation in aged mice. On the other hand, a major player promoting the plasticity of Foxp3 under inflammatory settings was found to be the transcriptional regulator Id2 [57], which when ectopically overexpressed in iTregs, sequesters the transcriptional regulator E protein E2A in the cytoplasm leading to generation of Th17 cells in Treg differentiation environment. A forced demethylation of Foxp3 Treg specific demethylated region, which is methylated in conventional T cells by agents like DNMT1 inhibitors as 5-aza-2-deoxycytidine (5-Aza) can stabilize the FOXP3 expression in Tregs [58,59].
miR-29b inhibits the progression of multiple myeloma through downregulating FOXP1
Published in Hematology, 2019
Hongyan Wang, Qiang Ding, Mingjun Wang, Mingwei Guo, Qi Zhao
FOXP1, a function gene associated with gene transcription and DNA repair, has been widely reported as oncogene or tumor suppressor gene involved in several cancers. For example, FOXP1 elicited a repressive effect on androgen receptor-induced transcriptional activity and acted as a tumor inhibitor as well as a prognostic factor in prostate cancer through inhibiting cell proliferation and migration [30]. Ectopic expression of FOXP1 was associated with unfavorable prognosis in neuroblastoma, and FOXP1 induction resulted in cell cycle arrest and apoptosis of neuroblastoma cells [31]. Knockdown of FOXP1 in ovarian cancer cells significantly decreased spheroid formation and tumor size in vivo by repressing cancer stem cell-like characteristics [32]. To further explore a novel regulatory mechanism of miR-29b in MM progression, in the following study, FOXP1 was identified to be a potential target gene of miR-29b, and the expression of FOXP1 was negatively modulated by miR-29b. Function and mechanism analyses revealed that restoration of FOXP1 weakened miR-29b-induced anti-proliferative and pro-apoptotic effects in MM cell lines.
How can we assess and measure prognosis for MALT lymphoma? A review of current findings and strategies
Published in Expert Review of Hematology, 2021
Barbara Kiesewetter, Markus Raderer
A translocation more recently detected is t(3;14)(p14.1;q32), involving fork head box protein 1 (FOXP1) as translocation partner for IGH and causing subsequent upregulation of FOXP1 expression [55]. FOXP1 expression was previously associated with poor prognosis in DLBCL, hence this was subsequently also evaluated in MALT lymphoma patients [56]. In a series of 70 patients, strong nuclear expression of FOXP1 was present in 29% (20/70) and was associated with higher relapse rates and shorter disease-free survival. The authors showed that patients with strong FOXP1 expression and additional presence of polymorphic histology, trisomy 3 and 18 had a higher risk for transformation to DLBCL.