新生物标志物可识别对精准治疗无反应的侵袭性淋巴瘤患者

  一个包括宾夕法尼亚大学医学部研究人员在内的团队发现了一个新的生物标志物,可以识别出不太可能对靶向治疗伊布替尼有反应的侵略性淋巴瘤患者。这是一个临床上可操作的发现,将有助于指导医生对那些携带BCL10基因中新暴露的突变的活化B细胞弥漫性大B细胞淋巴瘤(ABC-DLBCL)患者进行正确治疗。   这些发现是在12月6日第62届美国血液学会年会暨展览会的全体科学会议上公布的。宾夕法尼亚大学佩雷尔曼医学院Peter C. Nowell教授和个性化诊断中心主任Kojo S. J. Elenitoba-Johnson博士是共同作者。   ”Elenitoba-Johnson说:”这是一种以前没有得到充分重视的抗性机制。”伊布替尼本来是这类患者的候选药物,但如果他们有这些BCL10突变,应该优先考虑另一种治疗途径”。   伊布替尼是一种靶向治疗,它能阻断一种叫做 “布鲁顿酪氨酸激酶 “的蛋白质,它是帮助B细胞生长的途径的一部分。阻断BTK可以使B细胞,包括癌性B细胞,死亡或阻止它们分裂。这种药物已被证明对治疗复发和难治的淋巴瘤和白血病是有用的,但不是所有的。   研究人员发现,BCL10的突变促进了异常的信号传导途径,使细胞能够规避药物的阻断作用。   正常的BCL10与另外两种被称为CARD11和MALT1的蛋白质结合,以触发NF-kB信号,这在正常B细胞功能中很重要。然而,BCL10的突变颠覆了这一途径,而实现这一目的的机制并不十分清楚。研究人员利用一些复杂的技术,包括细胞电子显微镜,发现突变的BCL10可能与其他细胞的罪魁祸首联合起来,推动淋巴瘤的生长和对治疗的抵抗,但并不清楚这些是什么。   这就是宾夕法尼亚州医学会的研究人员深入的地方,他们在一种被称为基于质谱的蛋白质组分析的技术方面有很深的造诣,这种技术甚至可以进一步深入到蛋白质复合体的细微差别。他们发现了新的相互作用者–包括NF-κB2和TAB1–显示了细胞如何能够通过辅助信号来逃避药物。如果这个过程是一场接力赛,在一个 “正常 “的病人身上,药物会把第一个跑者手中的接力棒打掉,从而挫败癌症。但在这些突变的情况下,另一个团队的跑者会带着新的接力棒扑过来,帮助完成比赛。   Elenitoba-Johnson说:”切断上面的信号传递并不重要,因为这种蛋白质现在已经获得了一种新的能力,颠覆了药物能够有效地在怀有这些突变的淋巴瘤中发挥抑制作用的机制。   这些发现为不断增加的癌症遗传驱动因素清单增添了新的内容,继续有助于为淋巴瘤患者的治疗计划提供信息。DLBCL是成人淋巴瘤中最常见的亚型,在美国每年有超过25000个新病例。ABC-DLBCL是其最具侵略性的形式之一。   ”Elenitoba-Johnson说:”精准医疗是我们的目标,基于遗传学和其他因素的个体化治疗,让我们在正确的时间、正确的剂量为患者提供正确的药物。”识别这些新机制加强了这种类型的淋巴瘤患者的治疗方法。 本文来源于互联网,如有侵权请联系删除。来源:https://medicalxpress.com/news/2020-12-biomarker-patients-aggressive-lymphoma-dont.html

Introduction to lymphoma

Description: Lymphoma is a malignant tumor that originates in lymph nodes or lymphoid tissues. The clinical manifestations are painless and progressive lymphadenopathy. The disease can occur at any age, but the peak age of onset is 31 to 40 years old, and the peak of non-Hodgkin's lymphoma is slightly advanced. The ratio of male to female is: 2~3:1. Cause: The cause of human lymphoma is not clear. Only two viruses in humans are clearly associated with lymphoma, namely Epstein-Barr virus and human T-cell lymphoma/leukemia virus (HTLV-1). According to its pathological features, it is divided into Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). Symptoms: 1. Lymph node and lymphoid tissue onset The superficial lymph node is the majority, and HD is more than NHL. The affected lymph nodes are the most in the neck, followed by the infraorbital and groin. Generally painless, progressive swelling, moderate hardness. It is active in the early stage, and more adhesions occur in the late stage and multiple swollen lymph nodes merge into pieces. In some HD patients, lymphadenopathy can temporarily pause or even shrink at a certain time, so that it is misdiagnosed as lymphadenitis or lymphatic tuberculosis. Deep lymph node onset, mediastinal lymph nodes are more common, swollen lymph nodes can compress the superior vena cava, causing superior vena cava syndrome. It can also compress the trachea, esophagus, and recurrent laryngeal nerves and have symptoms such as difficulty breathing, difficulty swallowing, and hoarseness. Mediastinal NHL complicated by lymphosarcoma cell leukemia is more common. The HD of young women in the mediastinum is mostly nodular sclerosis, which is often unsatisfactory for the treatment response. Malignant lymphoma originating from the retroperitoneal lymph nodes is more common with NHL, which can cause long-term, unexplained fever, which makes clinical diagnosis difficult. Lymphoma that originates in the lymphatic ring of the pharynx is more common in the NHL and is often accompanied by an axillary invasion. Symptoms include sore throat, foreign body sensation, poor breathing, and hoarseness. Second, the onset of the disease in addition to lymphoid tissue, any part of the body can be affected, which is the most common in the gastrointestinal tract, stomach and high intestinal lymphoma may have upper abdominal pain, vomiting and other symptoms. Small intestinal lymphoma occurs in the ileocecal area, often with chronic diarrhea, steatorrhea, and intestinal obstruction. Third, systemic symptoms often have general weakness, weight loss, loss of appetite, night sweats and irregular fever. A small number of HDs can have periodic fever. Diagnosis: The so-called "plaque enlargement", whether it shows a malignant cancer disease, needs to be carefully distinguished, because some relatively non-risk diseases, such as lymph node inflammation or other infections, may also cause lymph gland enlargement, Therefore, when we first deal with lymphadenopathy, we must carefully examine the size, hardness, and skin lesions of the lymph glands, and from the patient's clinical process, the duration, size, and hardness of lymphadenopathy and including weight loss. There is no reason for fever or night sweats, as well as itchy skin and other symptoms to determine what it is. Complications: There were no obvious complications in the early stage of lymphoma, and the clinical manifestations of infection and corresponding tissue and organ invasion occurred in the late stage with the progression of the lesion. Treatment: The treatment of lymphoma has made significant progress in recent years, and most of HD can be cured. Although NHL is not as effective as HD, some cases have been cured. First, radiation therapy: (1) HD IA and IIA can be used alone in sub-lymphatic irradiation. (2) NHL low IA and IIA should be treated with chemotherapy after radiotherapy (January). Second, chemotherapy: (1) HDIIIB ~ V phase cases should be treated with chemotherapy, combined with chemotherapy regimen MOPP6 courses, complete remission rate can reach 60 ~ 80%, 1/2 ~ 1/3 cases to maintain long-term remission, and some long 15 years. (2) Low and moderate NHL stage III, VI and high-grade stage I~IV are suitable for chemotherapy. After the tumor is relieved, regional radiotherapy is performed as appropriate. Third, surgical treatment: the following conditions are feasible surgical radicalization, followed by radiotherapy and chemotherapy: 1 limited body surface extranodal lesions; 2 digestive tract lymphoma; 3 genitourinary lymphoma; 4 primary spleen lymph tumor. Fourth, bone marrow transplantation: the efficacy of bone marrow transplantation on lymphoma needs to be assessed. prevention: Read more...

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