The Granulocyte/Macrophage-Colony Stimulating Factor (GM-CSF): Basic Science and Clinical Application

Abstract

Granulocyte/Macrophage Colony Stimulating Factor (GM-CSF) stimulates the production as well as the function of myeloid cells, i.e. granulocytes and macrophages. Proliferative effects are exerted on the level of the multipotent as well as the unipotent progenitor cell. Functional effects on mature phagocytes comprise bactericidal and tumoricidal mechanisms including induction of cytokine release. GM-CSF receptors are present on normal hematopoietic progenitors as well as on mature granulocytes, on leukemic cells and some non-hematopoietic cells. Alteration of the GM-CSF gene has been associated with distinct features of AML and ALL. The glycosilated molecule is produced by various hemolymphopoietic and possibly non-hematopoietic cells, amongst whom T-lymphocytes and marrow stroma may be most relevant for myelopoiesis. The regulation of gene expression is exerted on both transcriptional and posttranscriptional levels of gene expression. GM-CSF production may play a role in steady state as well as in stress hematopoiesis. In vivo application of GM-CSF leads to a marked increase of phagocytes, in particular granulocytes. GM-CSF reduces the duration of neutropenia following aplasiogenic and ablative therapy. GM-CSF may possibly be helpful in the treatment of victims of radiation accidents and in patients with acquired neutropenias and glykogenosis IB. The curative potential for the underlying malignant disease is to be investigated in the present cooperative european Ewing's sarcoma study.

Bone marrow and peripheral white blood cells number is affected by sleep deprivation in a murine experimental model

“…There are many possible biological mechanisms underlying the changes induced by PSD. PSD for 72 h and stress can promote similar biological phenomena such as bone marrow hypocellularity, lymphopenia, neutrophilia, and monocytosis in the peripheral blood (Burdach, 1991; Lord et al, 1993; Engler et al, 2004; Engler et al, 2004; Dimitrov et al, 2009). However, PSD for 72 h by multiple platform method does not increase the serum levels of stress‐related factors (e.g., corticosterone) in C57BL/6 mice suggesting that activated hypothalamic–pituitary–adrenal axis has only a minor participation in the phenomenon caused by PSD in this model (Zager et al, 2009).…”

ARP, A Peptide Derived from the Stress-Associated Acetylcholinesterase Variant, Has Hematopoietic Growth Promoting Activities

“…Glucocorticoids evoke cascades culminating in the proliferation, differentiation, and apoptotic events characteristic of each of the hematopoietic cell lineages [for review see (6)]. In addition, glucocorticoid hormones mediate changes in the levels of hematopoietic growth factors that control the proliferation of hematopoietic stem cells (7,8).…”

FLT3 inhibitors upregulate CXCR4 and E-selectin ligands through suppression of ERK in AML and combined inhibition of CXCR4/E-selectin enhances anti-leukemia efficacy of FLT3-targeted therapy

“…HSCs and the extracellular matrix, including cytokines, are important components of the BMM that directly or indirectly modulate HSC differentiation. Normal hematopoiesis can be augmented by many cytokines, such as TPO, GM-CSF, G-CSF, and IL-3, which enhance HSCs differentiation and improve the e cacy of chemotherapy and targeted therapy in leukemia patients [42][43][44][45] . Our data showed a marked increase in TPO, GM-CSF, G-CSF, and IL-3 levels in leukemia cells after being exposed to sorafenib or the combination of sorafenib/GMI-1359 in hypoxia condition for 24 h (Fig.…”

“…Many cytokines, such as TPO, GM-CSF, G-CSF and IL-3, are associated with normal hematopoiesis and leukemia cell homing, and are also thought to be shared between leukemia and HSCs [42][43][44][45] . To better understand the mechanisms by which co-targeting CXCR4/E-selectin with GMI-1359 protects normal hematopoiesis, we further pro led these correlated cytokines using a Human Cytokine Antibody Array after exposing leukemia cells to GMI-1359 or sorafenib in an in vitro co-culture system under hypoxia conditions (Fig.…”