mRNA Expression Profiles in Human Lymphoid Progenitor Cell are Modified by High-dose Ionizing Radiation

Abstract

The treatment of lymphocytopenia induced by high-dose ionizing radiation (IR), a component of acute radiation syndrome (ARS), is an important issue in radiation emergency medicine. A limited stockpile of cytokines (hematopoietic stimulation factors) is recommended by the International Atomic Energy Agency in case of radiation disasters leading to high numbers of ARS cases. We hypothesized the presence of a radiosensitive target molecule specifically in lymphoid cells (the most radiosensitive lineage of hematopoietic cells) could improve treatment of ARS through pharmacological intervention. To examine this, human lymphoid progenitor mRNA from IM-9 cell was isolated and analyzed using cDNA microarray. The mRNA profiles demonstrated a strong correlation between IR and up-regulation of p53 signaling and 10 other molecules that together constituted a complete signaling pathway (TNFRSF10B, FAS, PIK3CG, BBC3, TP53I3, CDKN1A, JUN, MDM2, RRM2B, and TP53INP1). Only one member of this pathway, RB1, was found to be down-regulated. The induction of apoptosis and accumulation of G2/M cell cycle phase were observed following IR. These results identified that behavior of lymphoid progenitor cell following IR regulates apoptosis-related signaling and cell cyclerelated signaling by eleven mRNAs. In our next study phase, we aim to verify whether the alternation of these gene expressions is similarly observed in each lymphoid lineage (from immature progenitors to mature cells) and other radiosensitive cell types following IR, and whether gene expression control is possible in lymphoid cells.