CD52 is a molecular target in advanced systemic mastocytosis

被引：28

作者：

Hoermann, Gregor ^{[1
]}

Blatt, Katharina ^{[2
]}

Greiner, Georg ^{[1
]}

Putz, Eva Maria ^{[5
]}

Berger, Angelika ^{[5
]}

Herrmann, Harald ^{[6
]}

Cerny-Reiterer, Sabine ^{[2
,6
]}

Gleixner, Karoline V. ^{[2
]}

Walz, Christoph ^{[7
]}

Hoetzenecker, Konrad ^{[3
]}

Muellauer, Leonhard ^{[4
]}

Reiter, Andreas ^{[8
]}

Sotlar, Karl ^{[7
]}

Sexl, Veronika ^{[5
]}

Valent, Peter ^{[2
,6
]}

Mayerhofer, Matthias ^{[9
]}

机构：

[1] Med Univ Vienna, Dept Lab Med, Vienna, Austria

[2] Med Univ Vienna, Div Hematol & Hemostaseol, Dept Internal Med 1, Vienna, Austria

[3] Med Univ Vienna, Div Thorac Surg, Dept Surg, Vienna, Austria

[4] Med Univ Vienna, Dept Pathol, Vienna, Austria

[5] Univ Vet Med Vienna, Inst Pharmacol & Toxicol, Vienna, Austria

[6] Ludwig Boltzmann Cluster Oncol, Vienna, Austria

[7] Univ Munich, Inst Pathol, D-80539 Munich, Germany

[8] Univ Med Mannheim, Med Univ Klin, Mannheim, Germany

[9] Hanusch Hosp, Ludwig Boltzmann Inst Osteol, A-1140 Vienna, Austria

来源：

FASEB JOURNAL | 2014年 / 28卷 / 08期

基金：

奥地利科学基金会;

关键词：

CAMPATH-1; RAS G12V; alemtuzumab; mast cell leukemia; CHRONIC LYMPHOCYTIC-LEUKEMIA; MONOCLONAL-ANTIBODY CAMPATH-1H; NEOPLASTIC MAST-CELLS; C-KIT; THERAPEUTIC TARGET; CATALYTIC DOMAIN; ACTIVATING MUTATIONS; GENE-EXPRESSION; RAS ACTIVATION; ONCOSTATIN M;

D O I：

10.1096/fj.14-250894

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Advanced systemic mastocytosis (SM) is an aggressive hematopoietic neoplasm with poor prognosis and short survival times. So far, no curative therapy is available for affected patients. We have identified the cell surface antigen CD52 (CAMPATH-1) as a molecular target expressed abundantly on the surface of primary neoplastic mast cells (MCs) in patients with advanced SM. In contrast, neoplastic MCs of patients with indolent SM and normal MCs expressed only low levels or did not express CD52. To study the mechanisms of CD52 expression and the value of this antigen as a potential therapeutic target, we generated a human MC cell line, designated MCPV-1, by lentiviral immortalization of cord blood-derived MC progenitor cells. Functional studies revealed that activated RAS profoundly promotes surface expression of CD52. The CD52-targeting antibody alemtuzumab induced cell death in CD52(+) primary neoplastic MCs obtained from patients with SM as well as in MCPV-1 cells. NSG mice xenotransplanted with MCPV-1 cells survived significantly longer after treatment with alemtuzumab (median survival: 31 d untreated vs. 46 d treated; P = 0.0012). We conclude that CD52 is a novel marker and potential therapeutic target in neoplastic MCs in patients with advanced SM.

引用

页码：3540 / 3551

页数：12

共 55 条

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