The flow cytometry-defined light chain cytoplasmic immunoglobulin index and an associated 12-gene expression signature are independent prognostic factors in multiple myeloma

作     者：Papanikolaou, X. Alapat, D. Rosenthal, A. Stein, C. Epstein, J. Owens, R. Yaccoby, S. Johnson, S. Bailey, C. Heuck, C. Tian, E. Joiner, A. van Rhee, F. Khan, R. Zangari, M. Jethava, Y. Waheed, S. Davies, F. Morgan, G. Barlogie, B. 

作者机构：Univ Arkansas Med Sci Myeloma Inst Res & Therapy Little Rock AR 72205 USA Univ Arkansas Med Sci Dept Pathol Little Rock AR 72205 USA Canc Res & Biostat Seattle WA USA 

出 版 物：《LEUKEMIA》 (白血病)

年 卷 期：2015年第29卷第8期

页      面：1713-1720页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：National Cancer Institute [PO1 CA 55819] 

主　　题：Aged Biomarkers, Tumor/genetics Biomarkers, Tumor/metabolism Female Flow Cytometry/methods Flow Cytometry/methods Gene Expression Profiling Humans Immunoglobulin Light Chains/metabolism Male Multiple Myeloma/genetics Multiple Myeloma/genetics Multiple Myeloma/immunology Multiple Myeloma/immunology Multiple Myeloma/metabolism Multiple Myeloma/metabolism Multiple Myeloma/mortality Multiple Myeloma/mortality Neoplasm Staging Neoplasm Staging Oligonucleotide Array Sequence Analysis Prognosis Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger/genetics Survival Rate 

摘      要：As part of Total Therapy (TT) 3b, baseline marrow aspirates were subjected to two-color flow cytometry of nuclear DNA content and cytoplasmic immunoglobulin (DNA/CIG) as well as plasma cell gene expression profiling (GEP). DNA/CIG-derived parameters, GEP and standard clinical variables were examined for their effects on overall survival (OS) and progression-free survival (PFS). Among DNA/CIG parameters, the percentage of the light chain-restricted (LCR) cells and their cytoplasmic immunoglobulin index (CIg) were linked to poor outcome. In the absence of GEP data, low CIg = 65 years were significantly associated with inferior OS and PFS. When GEP information was included, low CIg survived the model along with GEP70-defined high risk and low albumin. Low CIg was linked to beta-2-microglobulin 45.5 mg/l, a percentage of LCR cells exceeding 50%, C-reactive protein = 8 mg/l and GEP-derived high centrosome index. Further analysis revealed an association of low CIg with 12 gene probes implicated in cell cycle regulation, differentiation and drug transportation from which a risk score was developed in TT3b that held prognostic significance also in TT3a, TT2 and HOVON trials, thus validating its general applicability. Low CIg is a powerful new prognostic variable and has identified potentially drug-able targets.