The cytokine/chemokine pattern in the bone marrow environment of multiple myeloma patients

被引：79

作者：

Cao, Yanran ^{[1
]}

Luetkens, Tim ^{[1
]}

Kobold, Sebastian ^{[1
]}

Hildebrandt, York ^{[2
]}

Gordic, Maja ^{[1
]}

Lajmi, Nesrine ^{[1
]}

Meyer, Sabrina ^{[1
]}

Bartels, Katrin ^{[1
]}

Zander, Axel R. ^{[2
]}

Bokemeyer, Carsten ^{[1
]}

Kroeger, Nicolaus ^{[2
]}

Atanackovic, Djordje ^{[1
]}

机构：

[1] Univ Med Ctr Hamburg Eppendorf, Univ Canc Ctr Hamburg, Hubertus Wald Tumorzentrum, Dept Internal Med Oncol Hematol Stem Cell Transpl, D-20246 Hamburg, Germany

[2] Univ Med Ctr Hamburg Eppendorf, Dept Stem Cell Transplantat, D-20246 Hamburg, Germany

来源：

EXPERIMENTAL HEMATOLOGY | 2010年 / 38卷 / 10期

关键词：

ENDOTHELIAL GROWTH-FACTOR; T-CELLS; C-MET; CHEMOKINES; EXPRESSION; CYTOKINE; ANGIOGENESIS; DISEASE; AUTOIMMUNITY; EOSINOPHILS;

D O I：

10.1016/j.exphem.2010.06.012

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective. The interaction of multiple myeloma (MM) with its bone marrow (BM) microenvironment is important for the homing pattern, survival, and proliferation of malignant plasma cells. We aimed at answering the question which cytokines, chemokines, and growth factors are typically found in the BM of untreated MM patients as well as in MM patients after allogeneic stem cell transplantation (alloSCT). Materials and Methods. We determined the concentrations of 34 cytokines/chemokines in the supernatants of 10 myeloma cell lines, as well as in the plasma derived from BM and peripheral blood samples of 10 newly diagnosed MM patients, 20 MM patients who had received allogeneic stem cell transplantation (alloSCT), and 20 healthy donors. Results. Besides cytokines/chemokines known to be secreted by myeloma cell lines, such as interleukin-1 receptor antagonist (IL-1RA), IL-8, monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, and MIP-3 alpha, we also detected significant levels of epidermal growth factor (EGF), hepatocyte growth factor (HGF), IL2R, IL-12p40/p70, IL-22, interferon-gamma (IFN-gamma) inducible protein 10 (IP-10), monokine induced by IFN-gamma (MIG), and regulated on activation normally T-cell expressed and secreted (RANTES) in culture supernatants. The BM environment in MM patients evidenced elevated concentrations of HGF, IL-2R, IL-16, EGF, IL-IRA, IP-10, MCP-1, and monokine induced by IFN-gamma. Additionally, in the BM of MM patients post alloSCT, we found selectively elevated concentration of IL-4, IL-6, IL-8, IL-12p40/p70, and eotaxin. Eotaxin levels were particularly high in patients with chronic graft-vs-host disease. Conclusions. Our study demonstrates characteristic cytokine/chemokine patterns in the BM environment of MM patients before and after alloSCT. Certain factors, such as MIP-1 alpha., MCP-1, HGF, IL-16, IP-10, and eotaxin, might not only be developed into diagnostic instruments and/or predictive biomarkers, but are also potential targets for future myeloma- or graft-vs-host disease specific therapies. (C) 2010 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.

引用

页码：860 / 867

页数：8

共 58 条

[41]

Pellegrino Antonio, 2002, Recenti Progressi in Medicina, V93, P642

[42] Vascular endothelial growth factor-induced migration of multiple myeloma cells is associated with β1 integrin- and phosphatidylinositol 3-kinase-dependent PKCα activation [J].