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

来源：

LEUKEMIA | 2008年 / 22卷 / 05期

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

页码：1044 / 1052

页数：9

共 47 条

[21]

Fonseca R, 2002, CANCER RES, V62, P715

[22] The t(4;14)(p16.3;q32) is strongly associated with chromosome 13 abnormalities in both multiple myeloma and monoclonal gammopathy of undetermined significance [J].

Fonseca, R ;

Oken, MM ;

Greipp, PR .

BLOOD, 2001, 98 (04) :1271-1272

[23] Clinical significance of the translocation (11;14)(q13;q32) in multiple myeloma [J].

Fonseca, R ;

Hoyer, JD ;

Aguayo, P ;

Jalal, SM ;

Ahmann, GJ ;

Rajkumar, SV ;

Witzig, TE ;

Lacy, MQ ;

Dispenzieri, A ;

Gertz, MA ;

Kyle, RA ;

Greipp, PR .

LEUKEMIA & LYMPHOMA, 1999, 35 (5-6) :599-605

[24] An update on conformation sensitive gel electrophoresis [J].

Ganguly, A .

HUMAN MUTATION, 2002, 19 (04) :334-342

[25] CONFORMATION-SENSITIVE GEL-ELECTROPHORESIS FOR RAPID DETECTION OF SINGLE-BASE DIFFERENCES IN DOUBLE-STRANDED PCR PRODUCTS AND DNA FRAGMENTS - EVIDENCE FOR SOLVENT-INDUCED BENDS IN DNA HETERODUPLEXES [J].

GANGULY, A ;

ROCK, MJ ;

PROCKOP, DJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (21) :10325-10329

[26] Primary plasma cell leukemia:: Clinical, immunophenotypic, DNA ploidy, and cytogenetic characteristics [J].

García-Sanz, R ;

Orfao, A ;

González, M ;

Tabernero, MD ;

Bladé, J ;

Moro, MJ ;

Fernández-Calvo, J ;

Sanz, MA ;

Pérez-Simón, JA ;

Rasillo, A ;

San Miguel, JF .

BLOOD, 1999, 93 (03) :1032-1037

[27] Clinical implications of t(11;14)(q13;q32), t(4;14)(p16.3;q32), and-17p13 in myeloma patients treated with high-dose therapy [J].

Gertz, MA ;

Lacy, MQ ;

Dispenzieri, A ;

Greipp, PR ;

Litzow, MR ;

Henderson, KJ ;

Van Wier, SA ;

Ahmann, GJ ;

Fonseca, R .

BLOOD, 2005, 106 (08) :2837-2840

[28] Translocations involving the immunoglobulin heavy-chain locus are possible early genetic events in patients with primary systemic amyloidosis [J].

Hayman, SR ;

Bailey, RJ ;

Jalal, SM ;

Ahmann, GJ ;

Dispenzieri, A ;

Gertz, MA ;

Greipp, PR ;

Kyle, RA ;

Lacy, MQ ;

Rajkumar, SV ;

Witzig, TE ;

Lust, JA ;

Fonseca, R .

BLOOD, 2001, 98 (07) :2266-2268

[29] Methylation-specific PCR: A novel PCR assay for methylation status of CpG islands [J].

Herman, JG ;

Graff, JR ;

Myohanen, S ;

Nelkin, BD ;

Baylin, SB .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (18) :9821-9826

[30] Loss of PTEN expression leading to high Akt activation in human multiple myelomas [J].

Hyun, T ;

Yam, A ;

Pece, S ;

Xie, XZ ;

Zhang, J ;

Miki, T ;

Gutkind, JS ;

Li, WQ .

BLOOD, 2000, 96 (10) :3560-3568

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