Genetic aberrations and survival in plasma cell leukemia

被引:211
作者
Tiedemann, R. E. [1 ]
Gonzalez-Paz, N. [2 ]
Kyle, R. A. [2 ]
Santana-Davila, R. [3 ]
Price-Troska, T. [2 ]
Van Wier, S. A. [1 ]
Chng, W. J. [1 ]
Ketterling, R. P. [4 ]
Gertz, M. A. [2 ]
Henderson, K. [2 ]
Greipp, P. R. [2 ]
Dispenzieri, A. [2 ]
Lacy, M. Q. [2 ]
Rajkumar, S. V. [2 ]
Bergsagel, P. L. [1 ]
Stewart, A. K. [1 ]
Fonseca, R. [1 ]
机构
[1] Mayo Clin, Arizona Canc Ctr, Div Hematol Oncol, Scottsdale, AZ 85259 USA
[2] Mayo Clin, Div Hematol, Rochester, MN USA
[3] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA
[4] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA
关键词
translocation; deletion; p53; cyclin D; RAS; MYC;
D O I
10.1038/leu.2008.4
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Plasma cell leukemia (PCL) is an aggressive and rare hematological malignancy that originates either as primary disease (pPCL) or as a secondary leukemic transformation (sPCL) of multiple myeloma (MM). We report here the genetic aberrations and survival of 80 patients with pPCL or sPCL and make comparisons with 439 cases of MM. pPCL presents a decade earlier than sPCL (54.7 vs 65.3 years) and is associated with longer median overall survival (11.1 vs 1.3 months; P < 0.001). 14q32 (IgH) translocations are highly prevalent in both sPCL and pPCL (82-87%); in pPCL IgH translocations almost exclusively involve 11q13 (CCND1), supporting a central etiological role, while in sPCL multiple partner oncogenes are involved, including 11q13, 4p16 (FGFR3/MMSET) and 16q23 (MAF), recapitulating MM. Both show ubiquitous inactivation of TP53 (pPCL 56%; sPCL 83%) by coding mutation or 17p13 deletion; complemented by p14ARF epigenetic silencing in sPCL (29%). Both show frequent N-RAS or K-RAS mutation. Poor survival in pPCL was predicted by MYC translocation (P = 0.006). Survival in sPCL was consistently short. Overall pPCL and sPCL are different disorders with distinct natural histories, genetics and survival.
引用
收藏
页码:1044 / 1052
页数:9
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