Title

An oral HemokineTM, alpha-methylhydrocinnamate, enhances myeloid and neutrophil recovery following irradiation in vivo

UMMS Affiliation

Department of Pediatrics, Division of Hematology/Oncology

Date

2-28-2017

Document Type

Article

Disciplines

Cell Biology | Hematology | Hemic and Lymphatic Diseases

Abstract

An oral therapeutic which reduces duration of cytopenias and is active following accidental radiation exposures is an unmet need in radiation countermeasures. Alpha methylhydrocinnamate (ST7) prolongs STAT-5 phosphorylation, reduces growth-factor dependency of multi-lineage cell lines, and stimulates erythropoiesis. Here, ST7 and its isomers were studied for their effects on myeloid progenitors and hematopoietic stem cells (HSCs) following radiation, in nonhuman primates, and murine irradiation models. Addition of ST7 or ST7-S increased CFU-GM production by 1.7-fold (p<0.001), reduced neutrophil apoptosis comparable to G-CSF, and enhanced HSC survival post-radiation by 2-fold, (p=0.028). ST7 and ST7-S administered in normal baboons increased ANC and platelet counts by 50-400%. In sub-lethally-irradiated mice, ANC nadir remained > 200/mm3 and neutropenia recovered in 6days with ST7 treatment and 18days in controls (p<0.05). In lethally-irradiated mice, marrow pathology at 15days was hypocellular (10% cellularity) in controls, but normal (55-75% cellularity) with complete neutrophil maturation with ST7-S treatment. Following lethal irradiation, ST7, given orally for 4days, reduced mortality, with 30% survival in ST7-animals vs 8% in controls, (p<0.05). Collectively, the studies indicate that ST7 and ST7-S enhance myeloid recovery post-radiation and merit further evaluation to accelerate hematologic recovery in conditions of radiation-related and other marrow hypoplasias.

Rights and Permissions

Citation: Blood Cells Mol Dis. 2017 Mar;63:1-8. doi: 10.1016/j.bcmd.2016.10.021. Epub 2016 Oct 31. Link to article on publisher's site

Related Resources

Link to Article in PubMed

PubMed ID

27888688