Plasma cell myeloma--new biological insights and advances in therapy.
Plasma cell myeloma--new biological insights and advances in therapy.
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DOI：
10.1182/blood.v73.4.865.bloodjournal734865
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发表时间：
1989-03
期刊：
影响因子：
20.3
通讯作者：
B. Barlogie;J. Epstein;P. Selvanayagam;R. Alexanian
中科院分区：
文献类型：
--
作者：
B. Barlogie;J. Epstein;P. Selvanayagam;R. Alexanian
浆细胞骨髓瘤是一种比其占优势的浆细胞的相对均匀性所表明的更复杂的肿瘤，其代表了正常B细胞分化的终末阶段。表型，分子和细胞遗传学数据有利于骨髓瘤干细胞在造血发育早期的存在，因此，在慢性髓细胞性白血病（CML）中，作为恶性转化靶点的原始恶性细胞与显性临床表型之间存在很远的距离。痕量的前B细胞、髓样细胞和T细胞与成熟B细胞表型共表达，这在正常B细胞分化中是未知的。与CML类似，疾病进展以疾病去分化为标志，偶尔伴有骨髓瘤蛋白产生和发展的停止，而不是具有高LDH或骨髓增生异常/急性髓性白血病（AML）综合征的髓外淋巴瘤样特征。即使在新诊断的骨髓瘤中，血清LDH水平的预后重要性表明早期存在具有“LDH表型”的肿瘤细胞，由于耐药性和增殖优势，其在疾病进展期间优先扩增。这些细胞的进一步表征可能提供关于多发性骨髓瘤个体发生的重要线索。骨髓瘤细胞表达许多不同生物信号的受体，这些信号可能可用于免疫毒素或放射性同位素治疗。浆细胞及其前体细胞还产生多种细胞因子，其中一些具有脓毒症自刺激功能（如IL-1、IL-5、IL-6）和/或与疾病表现相关（如IL-1和TNF-β作为OAF）。浆细胞丰富的细胞表达为理解基因激活机制和异常生长和分化的本质提供了线索。通过使用反映肿瘤质量（即血清B2 M水平）和生物学的新定量参数，已经改进了病理学相关分期系统的准确性。细胞和分子生物学的进一步研究（即，CAL-LA，H-ras）可能会揭示这些肿瘤细胞的特征，定义临床实体，对治疗的反应，和长期预后。尽管使用了更多的药物和更强化的治疗方案，但在预后方面缺乏重大进展，这证明对于具有高度有利预后的患者、高龄患者和由于其他重大医学问题而预期寿命短的患者，继续使用标准美法仑-泼尼松是合理的。然而，需要从根本上偏离标准实践，以改善具有不良风险特征的年轻患者的预后。（400字处截断摘要）
Plasma cell myeloma is a more complex neoplasm than suggested by the relative uniformity of its dominant plasma cells, which represent the terminal stage of normal B-cell differentiation. Phenotypic, molecular, and cellular genetic data favor the presence of a myeloma stem cell early in hematopoietic development so that, as in chronic myelogenous leukemia (CML), a far distance exists between the primordial malignant cell that was the target of malignant transformation and the dominant clinical phenotype. Traces of pre-B, myeloid, and T cells are coexpressed with the mature B-cell phenotype, an occurrence unknown in normal B-cell differentiation. Analogous to CML, disease progression is marked by disease dedifferentiation, occasionally with cessation of myeloma protein production and development instead of extramedullary lymphomalike features with high LDH or myelodysplasia/acute myelogenous leukemia (AML) syndromes. The prognostic importance of serum LDH levels even in newly diagnosed myeloma suggests the early presence of tumor cells with "LDH phenotype," which, as a result of drug resistance and proliferative advantage, expand preferentially during disease progression. Further characterization of these cells may provide important clues about the ontogeny of multiple myeloma. Myeloma cells express many receptors for different biological signals that might be exploitable for therapy with immunotoxins or radioisotopes. Plasma cells and their precursors also produce a variety of cytokines, some of which have putatively autostimulatory functions (eg, IL-1, IL-5, IL-6) and/or are related to disease manifestations (eg, IL-1 and TNF-beta as OAF). The wealth of cellular expression by plasma cells provides clues for understanding the mechanisms of gene activation and the nature of abnormal growth and differentiation. The accuracy of prognostically relevant staging systems has been refined with the use of new quantitative parameters that reflect tumor mass (ie, serum B2M levels) and biology. Further studies of cellular and molecular biology (ie, CAL-LA, H-ras) may reveal those tumor cell features that define clinical entities, response to therapy, and long-term prognosis. The lack of a major advance in prognosis despite the use of more drugs and more intensive regimens justifies the continued use of standard melphalan-prednisone for patients with a highly favorable prognosis, for the very aged, and for those with a short life expectancy due to other major medical problems. However, a radical departure from standard practice is required to improve the prognosis for younger patients with poor risk features.(ABSTRACT TRUNCATED AT 400 WORDS)