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High levels of FLT3-ligand in bone marrow and peripheral blood of patients with advanced multiple myeloma

N. Steiner, R. Hajek, S. Sevcikova, B. Borjan, K. Jöhrer, G. Göbel, G. Untergasser, E. Gunsilius,

. 2017 ; 12 (7) : e0181487. [pub] 20170720

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc17030676

INTRODUCTION: Multiple myeloma (MM) is still incurable due to resistance against various therapies. Thus, the identification of biomarkers predicting progression is urgently needed. Here, we evaluated four biomarkers in bone marrow and peripheral blood of MM patients for their prognostic significance. MATERIALS & METHODS: Bone marrow- and peripheral blood plasma levels of FLT3-L, soluble TIE2, endostatin, and osteoactivin were determined in patients with monoclonal gammopathy of undetermined significance (MGUS, n = 14/n = 4), patients with newly diagnosed MM (NDMM, n = 42/n = 31) and patients with relapsed/refractory MM (RRMM, n = 27/n = 16) by sandwich ELISA. RESULTS: Median FLT3-L expression increased from MGUS (58.77 pg/ml in bone marrow; 80.40 pg/ml in peripheral blood) to NDMM (63.15 pg/ml in bone marrow; 85.05 pg/ml in peripheral blood) and was maximal in RRMM (122 pg/ml in bone marrow; 160.47 pg/ml in peripheral blood; NDMM vs. RRMM p<0.001). A cut-off value of FLT3-L >92 pg/ml in bone marrow and >121 pg/ml in peripheral blood was associated with relapse or refractoriness in MM patients. FLT3-L was found to be a high predictive marker for discrimination between NDMM and RRMM as well in bone marrow as in peripheral blood (AUC 0.75 in bone marrow; vs 0.84 in peripheral blood). CONCLUSION: High levels of FLT3-L in bone marrow and peripheral blood of MM patients identify patients with progressive disease and are associated with relapse or refractoriness in MM patients. FLT3-L could be useful as a marker to identify RRMM patients and should be evaluated as target for future therapies.

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$a INTRODUCTION: Multiple myeloma (MM) is still incurable due to resistance against various therapies. Thus, the identification of biomarkers predicting progression is urgently needed. Here, we evaluated four biomarkers in bone marrow and peripheral blood of MM patients for their prognostic significance. MATERIALS & METHODS: Bone marrow- and peripheral blood plasma levels of FLT3-L, soluble TIE2, endostatin, and osteoactivin were determined in patients with monoclonal gammopathy of undetermined significance (MGUS, n = 14/n = 4), patients with newly diagnosed MM (NDMM, n = 42/n = 31) and patients with relapsed/refractory MM (RRMM, n = 27/n = 16) by sandwich ELISA. RESULTS: Median FLT3-L expression increased from MGUS (58.77 pg/ml in bone marrow; 80.40 pg/ml in peripheral blood) to NDMM (63.15 pg/ml in bone marrow; 85.05 pg/ml in peripheral blood) and was maximal in RRMM (122 pg/ml in bone marrow; 160.47 pg/ml in peripheral blood; NDMM vs. RRMM p<0.001). A cut-off value of FLT3-L >92 pg/ml in bone marrow and >121 pg/ml in peripheral blood was associated with relapse or refractoriness in MM patients. FLT3-L was found to be a high predictive marker for discrimination between NDMM and RRMM as well in bone marrow as in peripheral blood (AUC 0.75 in bone marrow; vs 0.84 in peripheral blood). CONCLUSION: High levels of FLT3-L in bone marrow and peripheral blood of MM patients identify patients with progressive disease and are associated with relapse or refractoriness in MM patients. FLT3-L could be useful as a marker to identify RRMM patients and should be evaluated as target for future therapies.
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$a Hajek, Roman $u Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic. Department of Hematology-Oncology, University Hospital Ostrava, Ostrava, Czech Republic.
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$a Sevcikova, Sabina $u Babak Myeloma Group, Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic. Department of Clinical Hematology, University Hospital Brno, Czech Republic.
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$a Borjan, Bojana $u Laboratory for Tumor Biology & Angiogenesis, Innsbruck Medical University, Innrain 66, Innsbruck, Austria. Tyrolean Cancer Research Institute, Innrain 66, Innsbruck, Austria.
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$a Jöhrer, Karin $u Tyrolean Cancer Research Institute, Innrain 66, Innsbruck, Austria.
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$a Göbel, Georg $u Department of Medical Statistics, Informatics and Health Economics, Innsbruck Medical University, Schöpfstr. 41, Innsbruck, Austria.
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$a Untergasser, Gerold $u Department of Internal Medicine V (Hematology and Medical Oncology), Innsbruck Medical University, Anichstr. 35, Innsbruck, Austria. Tyrolean Cancer Research Institute, Innrain 66, Innsbruck, Austria.
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$a Gunsilius, Eberhard $u Department of Internal Medicine V (Hematology and Medical Oncology), Innsbruck Medical University, Anichstr. 35, Innsbruck, Austria. Laboratory for Tumor Biology & Angiogenesis, Innsbruck Medical University, Innrain 66, Innsbruck, Austria.
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