Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
Hematology Unit, Department of Internal Medicine, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Clin Exp Metastasis. 2024 Dec;41(6):829-842. doi: 10.1007/s10585-024-10305-2. Epub 2024 Aug 20.
Multiple myeloma (MM) is a clinical disorder characterized by aberrant plasma cell growth in the bone marrow microenvironment. Globally, the prevalence of MM has been steadily increasing at an alarming rate. In the United States, more than 30,000 cases will be diagnosed in 2024 and it accounts for about 2% of cancer diagnoses and more than 2% of cancer deaths, more than double the worldwide figure. Both symptomatic and active MM are distinguished by uncontrolled plasma cell growth, which results in severe renal impairment, anemia, hypercalcemia, and bone loss. Multiple drugs have been approved by the FDA and are now widely used in clinical practice for MM. Although triplet and quadruplet induction regimens, autologous stem cell transplantation (ASCT), and maintenance treatment are used, MM continues to be an incurable illness characterized by relapses that may occur at various phases of its progression. MM patients with frailty, extramedullary disease, plasma cell leukemia, central nervous system recurrence, functional high risk, and the elderly are among those with the greatest current unmet needs. The high cost of care is an additional challenge. MM cells are highly protein secretary cells and thus are dependent on the activation of certain translation pathways. MM also has a high chance of altering ribosomal protein-encoding genes like MYC mutation. In this article we discuss the importance of ribosome biogenesis in promoting MM and RNA polymerase I inhibition as an upcoming treatment with potential promise for MM patients.
多发性骨髓瘤(MM)是一种临床疾病,其特征是骨髓微环境中异常的浆细胞生长。在全球范围内,MM 的患病率以惊人的速度稳步上升。在美国,2024 年将诊断出超过 30000 例病例,占癌症诊断的 2%左右,癌症死亡人数的 2%以上,是全球的两倍多。有症状和活动性 MM 的特征是浆细胞失控生长,导致严重的肾功能损害、贫血、高钙血症和骨质流失。FDA 已经批准了多种药物,目前广泛用于 MM 的临床实践。尽管使用了三联和四联诱导方案、自体干细胞移植(ASCT)和维持治疗,但 MM 仍然是一种无法治愈的疾病,其特点是复发,可能发生在其进展的各个阶段。虚弱、骨髓外疾病、浆细胞白血病、中枢神经系统复发、功能高危和老年 MM 患者是目前需求最大但尚未得到满足的患者。高治疗费用是另一个挑战。MM 细胞是高度分泌蛋白的细胞,因此依赖于某些翻译途径的激活。MM 还具有改变核糖体蛋白编码基因的高几率,如 MYC 突变。在本文中,我们讨论了核糖体生物发生在促进 MM 中的重要性以及 RNA 聚合酶 I 抑制作为一种有前途的 MM 患者治疗方法。