Fen Zhu's research while affiliated with University of Wisconsin–Madison and other places

Publications (19)

Article
Early growth response gene (EGR1) is a transcription factor known to be a downstream effector of B cell receptor signaling and Janus kinase 1 (JAK1) signaling in diffuse large B cell lymphoma (DLBCL). While EGR1 is characterized as a tumor suppressor in leukemia and multiple myeloma, the role of EGR1 in lymphoma is unknown. Here we demonstrate that...
Article
Full-text available
Regulation of the anti-apoptotic BCL2 protein determines cell survival and is frequently abnormal in B cell lymphomas. An evolutionarily conserved post-translational mechanism for over-expression of BCL2 in human B cell lymphomas and the BCL2 paralogue CED-9 in Caenorhabditis elegans results from loss-of-function mutations in human FBXO10 and its C...
Article
Targeting the JAK/STAT and BCL2 pathways in patients with relapsed/refractory T cell acute lymphoblastic leukemia (T-ALL) may provide an alternative approach to achieve clinical remissions. Ruxolitinib and venetoclax show a dose-dependent effect on T-ALL individually, but combination treatment reduces survival and proliferation of T-ALL in vitro. U...
Preprint
Full-text available
Regulation of the anti-apoptotic BCL2 protein determines cell survival and is frequently abnormal in B cell lymphomas. An evolutionarily conserved post-translational mechanism for over-expression of BCL2 in human B cell lymphomas and the BCL2 paralogue CED-9 in Caenorhabditis elegans results from loss-of-function mutations in human FBXO10 and its C...
Article
Full-text available
Signal transducer and activator of transcription 3 (STAT3) is an important and the most studied transcription factor in the Janus kinase (JAK)/STAT signaling pathway. STAT3 mediates the expression of various genes that play a critical role in many cellular and biological processes, such as cell proliferation, survival, differentiation, migration, a...
Article
Full-text available
PRMT5, which regulates gene expression by symmetric dimethylation of histones and non-histone target proteins, is overexpressed and plays a pathogenic role in many cancers. In diffuse large B cell lymphoma (DLBCL), the mechanisms of PRMT5 dysregulation and its role in lymphomagenesis remain largely unknown. Here we demonstrate that B cell receptor...
Preprint
Relapsed/refractory T cell acute lymphoblastic leukemia (T-ALL) is difficult to salvage especially in heavily pretreated patients, thus novel targeted agents are sorely needed. Hyperactivated JAK/STAT and BCL2 overexpression promote increased T-ALL proliferation and survival, and targeting these pathways with small molecule inhibitors like ruxoliti...
Conference Paper
T-cell acute lymphoblastic leukemia (T-ALL) is a hematologic malignancy that accounts for 25% of adult and 15% of pediatric acute lymphoblastic leukemia (ALL) cases. Relapsed or refractory T-ALL is difficult to salvage with chemotherapy, which causes long-term toxicity, and is often fatal. The JAK/STAT and BCL-2 pathways are upregulated in T-ALL an...
Conference Paper
T-cell acute lymphoblastic leukemia (T-ALL) is a hematologic malignancy that accounts for 25% of adult and 15% of pediatric acute lymphoblastic leukemia (ALL) cases. Relapsed or refractory T-ALL is difficult to salvage with chemotherapy, which causes long-term toxicity, and is often fatal. The JAK/STAT and BCL-2 pathways are upregulated in T-ALL an...
Article
Full-text available
Arginine methylation is a common posttranslational modification that governs important cellular processes and impacts development, cell growth, proliferation, and differentiation. Arginine methylation is catalyzed by protein arginine methyltransferases (PRMTs), which are classified as type I and type II enzymes responsible for the formation of asym...
Article
Full-text available
STAT3 is constitutively activated in many cancers and regulates gene expression to promote cancer cell survival, proliferation, invasion, and migration. In diffuse large B cell lymphoma (DLBCL), activation of STAT3 and its kinase JAK1 is caused by autocrine production of IL-6 and IL-10 in the activated B cell-like subtype (ABC). However, the gene r...
Article
JAKs are non-receptor tyrosine kinases that are generally found in association with cytokine receptors. In the canonical pathway, roles of JAKs have well been established in activating STATs in response to cytokine stimulation to modulate gene transcription. In contrast, a noncanonical role of JAK2 has recently been discovered, in which JAK2 in the...
Article
Full-text available
Janus kinases (JAKs) classically signal by activating STAT transcription factors but can also regulate gene expression by epigenetically phosphorylating histone H3 on tyrosine 41 (H3Y41-P). In diffuse large B-cell lymphomas (DLBCLs), JAK signaling is a feature of the activated B-cell (ABC) subtype and is triggered by autocrine production of IL-6 an...

Citations

... However, when the cell is stimulated by some physical and chemical factors, the rapid activation of Egr-1 allows cells to enter the proliferation phase from the resting phase, which in turn leads to cell proliferation (22,23). In tumor cells, the role of Egr-1 is more complex and can be expressed as an oncogene or tumor suppressor gene in different types of tumor, for example, Egr-1 promotes the malignant behaviors of LC cells (24), circCSPP1-miR-520h-Egr-1 activation axis lead to the progression of prostate tumor (25), and Egr-1 as a potential oncogene that promotes cell proliferation and defines Egr-1 as a new molecular target in DLBCL non-Hodgkin lymphomar (26). As far as proliferation and differentiation of leukemia cells are concerned, although there are some studies associating it with the inhibition of proliferation and induction of differentiation of leukemia cells (27,28), its role in the committed differentiation of leukemia cells into monocyte/macrophages is rarely reported. ...
... The CXCR4/CXCL12 axis was found to inhibit TAM polarization toward the M1 phenotype. Some preclinical studies have demonstrated that the CXCR4 inhibitor plerixafor improves the clinical scores of T-ALL (91). ...
... Thirdly, an interesting finding was the prevalence of the STAT-3 gene at 4% in NHL, but unknown for CVID (63, 100). STAT-3 is a signal transducer and activator of transcription that mediates cellular responses associated with interleukins and growth factors (101). Among its multiple functions, STAT-3 intervenes in the cell cycle by inducing the expression of critical genes for the progression from G1 to S phase, is involved in the response to activated FGFR1-4 and anti-inflammatory response, and modulates differentiation toward Th17 or regulatory (T Reg ) cells through IL-6 signaling cascade and on the promoters of several acute-phase protein genes. ...
... Arginine methylation is the most widespread post-translational modification that regulates cellular processes, cell growth, proliferation, and differentiation in a mammalian cell [1]. The reported nine human PRMTs (protein arginine methyltransferases) were further divided into three types (type-I, type-II, and type-III) based on resulting methylated arginine. ...
... The mTOR pathway is a critical pathway in cancer cell survival, proliferation and invasion and inhibition of mTOR activity has been shown to lead to decreased MM cell survival (Li et al., 2020). Interplay between mTOR and PRMT5 has already been identified in different cell types, including T-lymphocytes B-cell lymphoma and glioblastoma (Holmes et al., 2019;Webb et al., 2019;Zhu et al., 2019). We observed an opposite phenomenon in MM cells than previously described by Holmes et al. in glioblastoma, an aggressive type of brain malignancy (Holmes et al., 2019). ...
... Although a driver EGFR mutation was detected as a potential target for the treatment of her lung adenocarcinoma, the secondary lymphoma lacked indications for targeted drugs and was associated with several adverse factors for long-term survival, such as high IPI, extra-nodular disease, ABC subtype, dual expression of C-Myc and Bcl-2, 21-24 and TET2, 25 TNFAIP3, 26 and SGK1 mutations. 27 The incidence of concurrent lung cancer and lymphoma has increased in recent years. Both lung cancer and NHL are associated with higher risks of secondary malignancies of 36.7% 28 and 10.95%, respectively. ...
... The only rhythmic biological process dominated by both HCs and KCs is glucose homeostasis; HC enriched TGs (HNF1A, HNF4A, and ZBTB20) and KC enriched TGs (MEN1 and FOXO1) were associated with glycogen and energy storage 62−65 ( Figure S6B), which possessed high abundance in the night and low in the daytime, consistent with the catabolism storage in day−night cycle ( Figure S6D). Unlike other rhythmic processes, HC possessed three of the five TGs on liver glucose metabolism, while KCs possessed above half of the top enriched Meds and TFs (3/6 in Meds and 2/3 in TFs), more than the counterparts in HCs (null in Meds and 1/3 in TFs); furthermore, KC enriched STAT3 is associated with interferon production, 66 which regulates glucose homeostasis. 67 These results suggest KCs were the trigger to induced glucose homeostasis maintenance in HCs, which was in agreement with the PC making/NPC triggering theory as described previously. ...
... For leukaemia cancer our included datasets: GSE94453, a review of 5 control samples and 4 leukaemia cancer subjects from Acute Myeloid Leukemia (AML) cell (blood) tissue [29]; GSE107071, a review of 3 control samples and 3 leukaemia cancer subjects from AML cell (blood) tissue [29]. For Lymphoma cancer our included dataset: GSE106092, a review of 2 control samples and 4 Mantle Cell Lymphoma (MCL) cancer subjects from mantle cell line (blood) tissue [30]. MCL is a type of non-Hodgkin lymphoma. ...
... Further studies are warranted to address whether JAK3 associates with and phosphorylate Histone H3 in vivo and how this might modulate epigenetic regulation and transcription in malignant T cells. Nuclear translocation is often mediated through a nuclear localization sequence (NLS), which has been identified in JAK1 and is required for nuclear translocation of JAK1 in hematopoietic cancer cells [36]. We looked for potential NLS sequences in JAK3 but were unable to identify a relevant sequence through NLS mapper [37]. ...
... It has been shown that Janus kinase (JAK) signaling is deregulated in several hematologic malignancies [218]. Interestingly, Rui et al. [219] demonstrated that JAK1 contributes to tumor growth and survival of ABC-DLBCL cells through a regulatory mechanism dependent on phosphorylation of histone H3 at tyrosine 41, which supports the development of JAK1 inhibitors for ABC-DLBCL therapy. However, some contradictory data showed an increased risk of B-cell lymphoma development in patients treated with JAK inhibitors by the impairment of immune surveillance [220][221][222], highlighting the importance of assessing the clinical impact of these drugs. ...