Molecular pathogenesis of multiple myeloma and its premalignant precursor

被引：274

作者：

Kuehl, W. Michael ^{[2
]}

Bergsagel, P. Leif ^{[1
]}

机构：

[1] Mayo Clin, Coll Med, Ctr Comprehens Canc, Scottsdale, AZ 10021 USA

[2] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2012年 / 122卷 / 10期

关键词：

PLASMA-CELL LEUKEMIA; UNDETERMINED SIGNIFICANCE MGUS; INDEPENDENT RISK-FACTOR; LIGHT-CHAIN RATIO; KAPPA-B PATHWAY; MONOCLONAL GAMMOPATHY; RAS MUTATIONS; BONE-MARROW; GENE-EXPRESSION; FLOW-CYTOMETRY;

D O I：

10.1172/JCI61188

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Multiple myeloma is a monoclonal tumor of plasma cells, and its development is preceded by a premalignant tumor with which it shares genetic abnormalities, including universal dysregulation of the cyclin D/retinoblastoma (cyclin D/RB) pathway. A complex interaction with the BM microenvironment, characterized by activation of osteoclasts and suppression of osteoblasts, leads to lytic bone disease. Intratumor genetic heterogeneity, which occurs in addition to intertumor heterogeneity, contributes to the rapid emergence of drug resistance in high-risk disease. Despite recent therapeutic advances, which have doubled the median survival time, myeloma continues to be a mostly incurable disease. Here we review the current understanding of myeloma pathogenesis and insight into new therapeutic strategies provided by animal models and genetic screens.

引用

页码：3456 / 3463

页数：8

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