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

[11] Primary plasma cell leukaemia:: a report of 18 cases [J].

Costello, R ;

Sainty, D ;

Bouabdallah, R ;

Fermand, JP ;

Delmer, A ;

Diviné, M ;

Marolleau, JP ;

Gastaut, JA ;

Olive, D ;

Rousselot, P ;

Chaïbi, P .

LEUKEMIA RESEARCH, 2001, 25 (02) :103-107

[12] PTEN is inversely correlated with the cell survival factor Akt/PKB and is inactivated via multiple mechanisms in haematological malignancies [J].

Dahia, PLM ;

Aguiar, RCT ;

Alberta, J ;

Kum, JB ;

Caron, S ;

Sill, H ;

Marsh, DJ ;

Ritz, J ;

Freedman, A ;

Stiles, C ;

Eng, C .

HUMAN MOLECULAR GENETICS, 1999, 8 (02) :185-193

[13] PRIMARY PLASMA-CELL LEUKEMIA [J].

DIMOPOULOS, MA ;

PALUMBO, A ;

DELASALLE, KB ;

ALEXANIAN, R .

BRITISH JOURNAL OF HAEMATOLOGY, 1994, 88 (04) :754-759

[14]

DREWINKO B, 1981, BLOOD, V57, P333

[15] GROWTH KINETICS OF PLASMA-CELL MYELOMA [J].

DREWINKO, B ;

ALEXANIAN, R .

JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1977, 58 (05) :1247-1253

[16]

Esteller M, 2001, CANCER RES, V61, P2816

[17] Mdm2 overexpression and p14ARF inactivation are two mutually exclusive events in primary human lung tumors [J].

Eymin, B ;

Gazzeri, S ;

Brambilla, C ;

Brambilla, E .

ONCOGENE, 2002, 21 (17) :2750-2761

[18] The recurrent IgH translocations are highly associated with nonhyperdiploid variant multiple myeloma [J].

Fonseca, R ;

Debes-Marun, CS ;

Picken, EB ;

Dewald, GW ;

Bryant, SC ;

Winkler, JM ;

Blood, E ;

Oken, MM ;

Santana-Dávila, R ;

González-Paz, N ;

Kyle, RA ;

Gertz, MA ;

Dispenzieri, A ;

Lacy, MQ ;

Greipp, PR .

BLOOD, 2003, 102 (07) :2562-2567

[19] Clinical and biologic implications of recurrent genomic aberrations in myeloma [J].

Fonseca, R ;

Blood, E ;

Rue, M ;

Harrington, D ;

Oken, MM ;

Kyle, RA ;

Dewald, GW ;

Van Ness, B ;

Van Wier, SA ;

Henderson, KJ ;

Bailey, RJ ;

Greipp, PR .

BLOOD, 2003, 101 (11) :4569-4575

[20] Genomic abnormalities in monoclonal gammopathy of undetermined significance [J].

Fonseca, R ;

Bailey, RJ ;

Ahmann, GJ ;

Rajkumar, SV ;

Hoyer, JD ;

Lust, JA ;

Kyle, RA ;

Gertz, MA ;

Greipp, PR ;

Dewald, GW .

BLOOD, 2002, 100 (04) :1417-1424

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