A Novel Cytological Model of B-Cell/Macrophage Biphenotypic Cell Hodgkin Lymphoma in Ganp-Transgenic Mice

Sakai, Yasuhiro; Rezano, Andri; Okada, Seiji; Ohtsuki, Takahiro; Kawashima, Yoshiaki; Tsukamoto, Tetsuya; Suzuki, Motoshi; Kohara, Michinori; Takeya, Motohiro; Sakaguchi, Nobuo; Kuwahara, K.

doi:10.3390/cancers12010204

Cited by 9 publications

(14 citation statements)

References 27 publications

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“…( 8 – 10 ). Moreover, the role of IL-10 in Hodgkin’s lymphoma, diffuse large B-cell lymphoma (DLBCL) and Burkitt’s lymphoma had also been extensively studied ( 11 , 12 ). However, little is known about the effects of IL-10 on response and prognosis, especially the early recurrence or progression of PTCL patients.…”

Section: Introductionmentioning

confidence: 99%

Increased Serum Level of Interleukin-10 Predicts Poor Survival and Early Recurrence in Patients With Peripheral T-Cell Lymphomas

et al. 2020

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Peripheral T cell lymphoma (PTCL) is an alloplasm group of aggressive and lymphoproliferative tumors with heterogeneous morphological changes of mature T cell immunophenotype. It has multiple subtypes and most of them have poor prognosis. Interleukin 10 (IL-10) is one kind of multi-cell-derived and multifunctional cytokine. It regulates the growth and differentiation of cells, participates in inflammation and immune response, plays an important role in tumor and infection, and is closely related to blood system diseases. Therefore, we implemented a retrospective study of 205 patients who were newly diagnosed with PTCL to explore the relationship between IL-10 and prognosis and early recurrence. We found patients with IL-10 ≥3.6 pg/ml achieved a lower CR rate and higher 1-year recurrence rate than patients with IL-10 <3.6 pg/ml (14.4 vs. 51.9%; 17.6 vs. 49.5%). On multivariate analysis, moreover, elevated IL-10 is an extremely important prognostic factor in PTCL, which can lead to worsening of overall survival (OS), low complete response (CR) rate and higher early relapse rate. Therefore, measurement of IL-10 levels in peripheral blood at the initial stage are useful for predicting the prognosis and helping us to make different treatment plans for individual patients. In the near future, IL-10 inhibitors or antagonists may become a new method of immunotargeting therapy for patients with PTCL.

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Section: Introductionmentioning

confidence: 99%

Increased Serum Level of Interleukin-10 Predicts Poor Survival and Early Recurrence in Patients With Peripheral T-Cell Lymphomas

et al. 2020

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“…GANP is a unique protein, the functions of which include mRNA nuclear export and B‐cell maturation 24,25 . We previously demonstrated the overexpression of proteins from the GANP/Sac3 family in lymphomas, melanomas, and liver fluke‐associated cholangiocarcinomas; and underexpression in breast cancers and glioblastomas 18,26–30 .…”

Section: Discussionmentioning

confidence: 99%

“…23 GANP is a unique protein, the functions of which include mRNA nuclear export and B-cell maturation. 24,25 We previously demonstrated the overexpression of proteins from the GANP/Sac3 family in lymphomas, melanomas, and liver fluke-associated cholangiocarcinomas; and underexpression in breast cancers and glioblastomas. 18,[26][27][28][29][30] Aberrant GANP expression contributes to the formation of abnormal DNA, creating an RNA hybrid structure named R-loop during transcription, and causing DNA damage and tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

Testicular teratomagenesis from primordial germ cells with overexpression of germinal center‐associated nuclear protein

et al. 2022

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Testicular teratomas are the major histologic type of testicular germ cell tumors and their incidence continues to grow. Moreover, teratomas can develop from undifferentiated cells in induced pluripotent stem (iPS) cell transplantation therapy, seriously hampering the progress of regenerative medicine. Germinal center‐associated nuclear protein (GANP) is thought to be important to the biogenetic control of primordial germ cells and is among the genes susceptible to testicular germ cell tumors. Thus, we analyzed the expression of GANP in human testicular postpubertal‐type teratomas and established a novel mouse model to reveal the association between GANP and teratomagenesis. We analyzed 31 cases of human testicular postpubertal‐type teratomas and, in all cases, GANP was overexpressed. The aberrant expression was also detected in germ cell neoplasia in situ accompanied by the teratoma. GANP expression was particularly high in the epithelia of the epidermis, cutaneous appendages, and trachea‐like ciliated epithelium. To further clarify the association between GANP and teratomagenesis, we established a novel teratomagenesis mouse model (CAG‐ganpTg mice). In the GANP−teratoma mice, GANP‐overexpressing teratomas were more frequent at the testes and the middle portion of the uterus than has been seen in the previously established mouse models. In conclusion, GANP is overexpressed in testicular postpubertal‐type teratomas and is an essential teratomagenic factor. We also found that CAG‐ganpTg mice are useful mouse models of teratomagenesis that mimics human midline teratomas and that teratomas may originate from the overexpression of GANP in primordial germ cells.

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“…GANP was initially identified as an abundant protein in splenic germinal centers, which are responsible for development of B cells [30], and subsequently the role of GANP has been extensively characterized in the context of B cell affinity maturation [46]. The recognition of (which was not certified by peer review) is the author/funder.…”

Section: Discussionmentioning

confidence: 99%

Peripheral neuropathy linked mRNA export factor GANP reshapes gene regulation in human motor neurons

Woldegebriel

Kvist

White

et al. 2021

Preprint

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Loss-of-function of the mRNA export protein GANP (MCM3AP gene) cause early-onset sensorimotor neuropathy, characterised by axonal degeneration in long peripheral nerves. GANP functions as a scaffold at nuclear pore complexes, contributing to selective nuclear export of mRNAs. Here, we aimed to identify motor neuron specific transcripts that are regulated by GANP and may be limiting for local protein synthesis in motor neuron axons. We compared motor neurons with a gene edited mutation in the Sac3 mRNA binding domain of GANP to isogenic controls. We also examined patient-derived motor neurons. RNA sequencing of motor neurons as well as nuclear and axonal subcompartments showed that mutant GANP had a profound effect on motor neuron transcriptomes, with alterations in nearly 40 percent of all expressed genes and broad changes in splicing. Expression changes in multiple genes critical for neuronal functions, combined with compensatory upregulation of protein synthesis and early-stage metabolic stress genes, indicated that RNA metabolism was abnormal in GANP-deficient motor neurons. Surprisingly, limited evidence was found for large-scale nuclear retention of mRNA. This first study of neuropathy-linked GANP defects in human motor neurons shows that GANP has a wide gene regulatory role in a disease-relevant cell type that requires long-distance mRNA transport.

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A Novel Cytological Model of B-Cell/Macrophage Biphenotypic Cell Hodgkin Lymphoma in Ganp-Transgenic Mice

Cited by 9 publications

References 27 publications

Increased Serum Level of Interleukin-10 Predicts Poor Survival and Early Recurrence in Patients With Peripheral T-Cell Lymphomas

Increased Serum Level of Interleukin-10 Predicts Poor Survival and Early Recurrence in Patients With Peripheral T-Cell Lymphomas

Testicular teratomagenesis from primordial germ cells with overexpression of germinal center‐associated nuclear protein

Peripheral neuropathy linked mRNA export factor GANP reshapes gene regulation in human motor neurons

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