Erythropoietin treatment in murine multiple myeloma: Immune gain and bone loss

Naamit Deshet-Unger, Sahar Hiram-Bab, Yasmin Haim-Ohana, Moshe Mittelman, Yankel Gabet, Drorit Neumann

نتاج البحث: نشر في مجلةمقالةمراجعة النظراء

ملخص

Multiple myeloma (MM) is a plasma cell malignancy, characterized by osteolytic lesions and monoclonal immunoglobulins. The anemia, accompanying the disease is often treated with recombinant human EPO. Diverse non-erythropoietic effects of EPO have led us to question its combined action on the immune system and bone in the 5T33MM mouse model. EPO administration to MM mice attenuated disease progression as demonstrated by a decrease in serum MM IgG2b, splenic CD138 expressing cells, IL-6 and RORÎ 3Ï., transcripts in bone marrow (BM). IFN-Î 3 transcript levels and macrophages (F4/80 + CD11b +) in the BM both increased ∼1.5 fold in the EPO-treated MM mice. In-vitro, EPO stimulated phagocytosis of 5T33MM cells (+30%) by BM-derived macrophages. In contrast, high-resolution microCT analysis of distal femurs revealed EPO-associated bone loss in both healthy and 5T33MM mice. EPO significantly increased expression of the osteoclastogenic nuclear factor-kappa B ligand (RANKL) in healthy mice, but not in MM mice, likely due to antagonizing effects on MM progression. Thus, in MM, EPO may act as a double-edged-sword stimulating immune response, while accelerating bone resorption, possibly via direct action on BM macrophages. This study supports a prudent approach of treating anemia in MM patients, aiming to maintain EPO-associated anti-MM effects, while considering bone damage.

اللغة الأصليةالإنجليزيّة
رقم المقال30998
دوريةScientific Reports
مستوى الصوت6
المعرِّفات الرقمية للأشياء
حالة النشرنُشِر - 2 أغسطس 2016

All Science Journal Classification (ASJC) codes

  • !!General

بصمة

أدرس بدقة موضوعات البحث “Erythropoietin treatment in murine multiple myeloma: Immune gain and bone loss'. فهما يشكلان معًا بصمة فريدة.

قم بذكر هذا