更新于：2024-11-01

C-Myc positive High grade B-cell lymphoma

C-Myc阳性高级别B细胞淋巴瘤

更新于：2024-11-01

基本信息

别名-

简介-

关联

项与 C-Myc阳性高级别B细胞淋巴瘤相关的药物

WBC100

靶点

c-Myc

作用机制

MYC基因抑制剂

在研机构

原研机构

在研适应症

非在研适应症

最高研发阶段临床1期

首次获批国家/地区-

首次获批日期1800-01-20

项与 C-Myc阳性高级别B细胞淋巴瘤相关的临床试验

NCT01914718 / Terminated临床2期IIT

Dose-adjusted EPOCH-R in Patients With Diffuse Large B-cell Lymphoma: a Phase II Study

The aim of this study is to evaluate the efficacy and toxicity of dose-adjusted EPOCH-R in patients with MYC positive diffuse large B-cell lymphoma.

开始日期2013-02-01

申办/合作机构

复旦大学

100 项与 C-Myc阳性高级别B细胞淋巴瘤相关的临床结果

登录后查看更多信息

100 项与 C-Myc阳性高级别B细胞淋巴瘤相关的转化医学

登录后查看更多信息

0 项与 C-Myc阳性高级别B细胞淋巴瘤相关的专利（医药）

登录后查看更多信息

项与 C-Myc阳性高级别B细胞淋巴瘤相关的文献（医药）

2023-12-01·Pathology

TdT-positive high-grade B-cell lymphoma with BCOR and IDH1 mutations

Letter

作者: Yu, Yu-Ting ; Chen, Yi-Lin ; Chang, Kung-Chao ; Medeiros, L Jeffrey ; Lin, Kuan-Yu ; Chen, Ya-Ping

2023-11-09·Cancer Research Communications

Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription

Article

作者: Izumi, Raquel ; Frigault, Melanie M ; Hamdy, Ahmed ; Johnson, Amy J ; Huang, Xin ; Wong, Harvey ; Mandava, Vinay ; Mithal, Arushi ; Birkett, Joseph ; Stelte-Ludwig, Beatrix

AbstractDouble-hit diffuse large B-cell lymphoma (DH-DLBCL) is an aggressive, and often refractory, type of B-cell non–Hodgkin lymphoma (NHL) characterized by rearrangements in MYC and BCL2. Cyclin-dependent kinase 9 (CDK9) regulates transcriptional elongation and activation of transcription factors, including MYC, making it a potential targeted approach for the treatment of MYC+ lymphomas. Enitociclib is a well-tolerated and clinically active CDK9 inhibitor leading to complete metabolic remissions in 2 of 7 patients with DH-DLBCL treated with once weekly 30 mg intravenous administration. Herein, we investigate the pharmacodynamic effect of CDK9 inhibition in preclinical models and in blood samples from patients [DH-DLBCL (n = 10) and MYC+ NHL (n = 5)] treated with 30 mg i.v. once weekly enitociclib. Enitociclib shows significant regulation of RNA polymerase II Ser2 phosphorylation in a MYC-amplified SU-DHL-4 cell line and depletion of MYC and antiapoptosis protein MCL1 in SU-DHL-4 and MYC-overexpressing SU-DHL-10 cell lines in vitro. Tumor growth inhibition reaching 0.5% of control treated SU-DHL-10 xenografts is achieved in vivo and MYC and MCL1 depletion as well as evidence of apoptosis activation after enitociclib treatment is demonstrated. An unbiased analysis of the genes affected by CDK9 inhibition in both cell lines demonstrates that RNA polymerase II and transcription pathways are primarily affected and novel enitociclib targets such as PHF23 and TP53RK are discovered. These findings are recapitulated in blood samples from enitociclib-treated patients; while MYC downregulation is most robust with enitociclib treatment, other CDK9-regulated targets may be MYC independent delivering a transcriptional downregulation via RNA polymerase II.Significance:MYC+ lymphomas are refractory to standard of care and novel treatments that downregulate MYC are needed. The utility of enitociclib, a selective CDK9 inhibitor in this patient population, is demonstrated in preclinical models and patients. Enitociclib inhibits RNA polymerase II function conferring a transcriptional shift and depletion of MYC and MCL1. Enitociclib intermittent dosing downregulates transcription factors including MYC, providing a therapeutic window for durable responses in patients with MYC+ lymphoma.

2023-07-01·Virchows Archiv

Losing CD45 and various B-cell markers in a case of MYC-driven pediatric high-grade B-cell lymphoma, not otherwise specified that transformed from Burkitt’s lymphoma during rituximab-containing treatments: a case report

Article

作者: Fu, Libing ; Luo, Yiyang ; Rao, Wei ; Cao, Zheng ; He, Lejian ; Xue, Xuemin ; Feng, Xiaoli ; Qiu, Tian ; Wang, Xiaojun

In this study, we reported a seldom case of pediatric high-grade B-cell lymphoma, not otherwise specified (HGBL, NOS) with loss of B-cell markers (CD19, CD20, CD22, CD79a, CD38, Pax5, OCT2, and BOB1) and CD45, which bring great challenges to exclude a non-lymphomatous neoplasm. However, no evidence was found to support the diagnosis of sarcoma and carcinoma. Thus, due to the patient's prior history of Burkitt's lymphoma treated by rituximab-containing therapies, we carefully searched for any indication of B-cell differentiation. Eventually, NGS results revealed the monoclonal rearrangement of IGH (IGHD2-8-IGHJ6 and IGHV4-30-2-IGHJ4) in both pre-treatment and present tumors, confirming the same B-cell lineage. Moreover, both tumors exhibited the same IGHA1-MYC translocation and somatic mutations of c-MYC, TP53, ID3, and CCND3. Therefore, in addition to strong expression of BCL2 in the present tumor, we finally arrived at a diagnosis of pediatric HGBL, NOS with loss of B-cell lineage markers and CD45.