Proliferation is a central independent prognostic factor and target for personalized and risk-adapted treatment in multiple myeloma
Proliferation is a central independent prognostic factor and target for personalized and risk-adapted treatment in multiple myeloma
复制标题
DOI：
10.3324/haematol.2010.030296
复制
发表时间：
2011-01-01
期刊：
影响因子：
--
通讯作者：
Goldschmidt, Hartmut
中科院分区：
文献类型：
--
作者：
Hose, Dirk;Reme, Thierry;Goldschmidt, Hartmut
恶性浆细胞的增殖是多发性骨髓瘤的一个强烈的不良预后因素，同时也是现有的(如微管蛋白聚合酶抑制剂)和即将到来的(如极光激酶抑制剂)化合物的靶点。设计与方法我们使用基于基因表达的指数来评估757个样本的增殖情况，包括来自先前未接受大剂量化疗的患者的298个和345个CD138纯化的骨髓瘤细胞的独立队列，以及临床预后因素、染色体异常和基于基因表达的高危评分。结果在这两个队列中，43.3%和39.4%的骨髓瘤细胞样本的增殖指数高于正常骨髓浆细胞的中位数加3个标准差。晚期患者、疾病进展相关基因1q21缺失或13q14.3缺失患者的恶性浆细胞增殖指数显著高于9、15、19号染色体(超二倍体)患者。在中期细胞遗传学中，细胞增殖与染色体异常的存在有关。在两个队列中，无事件生存期和总生存期都有显著的预测性，允许进行高度预测性的风险分层(例如，无事件生存期12.7个月对26.2个月对40.6个月，P
BackgroundProliferation of malignant plasma cells is a strong adverse prognostic factor in multiple myeloma and simultaneously targetable by available (e.g. tubulin polymerase inhibitors) and upcoming (e.g. aurora kinase inhibitors) compounds.Design and MethodsWe assessed proliferation using gene expression-based indices in 757 samples including independent cohorts of 298 and 345 samples of CD138-purified myeloma cells from previously untreated patients undergoing high-dose chemotherapy, together with clinical prognostic factors, chromosomal aberrations, and gene expression-based high-risk scores.ResultsIn the two cohorts, 43.3% and 39.4% of the myeloma cell samples showed a proliferation index above the median plus three standard deviations of normal bone marrow plasma cells. Malignant plasma cells of patients in advanced stages or those harboring disease progression-associated gain of 1q21 or deletion of 13q14.3 showed significantly higher proliferation indices; patients with gain of chromosome 9, 15 or 19 (hyperdiploid samples) had significantly lower proliferation indices. Proliferation correlated with the presence of chromosomal aberrations in metaphase cytogenetics. It was significantly predictive for event-free and overall survival in both cohorts, allowed highly predictive risk stratification (e.g. event-free survival 12.7 versus 26.2 versus 40.6 months, P