GM-CSF treatment is not effective in congenital neutropenia patients due to its inability to activate NAMPT signaling

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• 作者：Corinna Koch ; Bardia Samareh ; Tatsuya Morishima ; Perihan Mir…
• 关键词：Severe congenital neutropenia ; G ; CSF ; GM ; CSF ; NAMPT
• 刊名：Annals of Hematology
• 出版年：2017
• 出版时间：March 2017
• 年：2017
• 卷：96
• 期：3
• 页码：345-353
• 全文大小：
• 刊物类别：Medicine
• 刊物主题：Hematology; Oncology;
• 出版者：Springer Berlin Heidelberg
• ISSN：1432-0584
• 卷排序：96

文摘

Severe congenital neutropenia (CN) is a bone marrow failure syndrome characterized by an absolute neutrophil count (ANC) below 500 cells/μL and recurrent, life-threatening bacterial infections. Treatment with granulocyte colony-stimulating factor (G-CSF) increases the ANC in the majority of CN patients. In contrary, granulocyte-monocyte colony-stimulating factor (GM-CSF) fails to increase neutrophil numbers in CN patients in vitro and in vivo, suggesting specific defects in signaling pathways downstream of GM-CSF receptor. Recently, we detected that G-CSF induces granulopoiesis in CN patients by hyperactivation of nicotinamide phosphoribosyl transferase (NAMPT)/Sirtuin 1 signaling in myeloid cells. Here, we demonstrated that, in contrast to G-CSF, GM-CSF failed to induce NAMPT-dependent granulopoiesis in CN patients. We further identified NAMPT signaling as an essential downstream effector of the GM-CSF pathway in myelopoiesis.