Stewart A Keith, Fonseca Rafael
Hematology-Oncology, Room 3-008, Mayo Clinic College of Medicine, Scottsdale, AZ 85259, USA.
J Clin Oncol. 2005 Sep 10;23(26):6339-44. doi: 10.1200/JCO.2005.05.023.
Molecular diagnostic tools and novel therapeutics now offer the potential for accurate prognostic and personalized treatment road maps for patients with multiple myeloma (MM). We will review the evidence and provide specific recommendations for routine clinical molecular genetic testing and use of such information to guide therapeutic decision making. In particular, the negative prognostic impact of specific IgH translocations such as the t(4;14), t(14;16), chromosome 13 deletion by conventional cytogenetics and loss of 17p13 by interphase fluorescence in situ hybridization are now established. Preliminary gene expression profiling studies have also demonstrated that individual genes (CSK1-B) or groups of genes can define prognosis with greater accuracy than conventional genetic markers and can provide pharmacogenomic and biologic insight into the pathophysiology, therapeutics, and future targets of myeloma. Importantly, we recommend that all clinical trials now adopt routine genetic testing and risk stratification.
分子诊断工具和新型疗法如今为多发性骨髓瘤（MM）患者提供了制定准确预后和个性化治疗路线图的可能性。我们将回顾相关证据，并针对常规临床分子遗传学检测以及利用此类信息指导治疗决策提供具体建议。特别是，特定免疫球蛋白重链（IgH）易位如t(4;14)、t(14;16)的不良预后影响，通过传统细胞遗传学检测发现的13号染色体缺失以及间期荧光原位杂交检测发现的17p13缺失，如今已得到证实。初步的基因表达谱研究还表明，单个基因（CSK1 - B）或基因组能够比传统遗传标志物更准确地界定预后，并且能够为骨髓瘤的病理生理学、治疗方法及未来靶点提供药物基因组学和生物学方面的见解。重要的是，我们建议现在所有的临床试验都应采用常规基因检测和风险分层。
