It is note worthy that the number of BMNCs begins to increase at approximate 3 DAI and the recovery of WBCs and PLTs exhibit little delay. The results suggest that AP24534 Src-bcr-Abl inhibitor damaged bone marrow and hematopoietic function begin to recovery at approximately 3 DAI. To investigate gene expression profiles that are associated with BM recovery, mRNA expression in total bone marrow cells was profiled using gene chip at 3, 7, 11 and 21 DAI compared to 0 DAI as control. A total of 1302 genes were identified that showed statistically significant differential expression in irradiated mice at least at one time point when compared to control . A subset of these genes is known to have functions that are directly related to HSC selfrenewal. By comparing our results with HSC self-renewal and proliferation associated genes reported by Kirouac et al. , we identified eleven differentially expressed genes in common, ADIPOQ, CCL3, CCND1, CCND2, CDKN1A, CXCL12, JUNB, PTEN, TAL1, THY1 and TNF. Our data show that Adipoq and Cxcl12 were up-regulated, which is known to increase HSC proliferation; conversely, Ccl3 and Tnf were down-regulated, which is known to repress HSC proliferation . Based on these data, cell-extrinsic and cell-intrinsic regulation networks can be constructed, which are expected to be comprised of genes that regulate damaged bone marrow regeneration and have a central role in the control of HSC proliferation. The temporal expression pattern of significant differential gene expression was examined by using STEM software, each profile contains a cluster of multiple genes which have similar expression patterns after IR . Eleven significant clusters containing a total of 686 genes were identified . Six of these clusters are comprised of genes that were repressed at early time points and then gradually elevated expression levels at later time points, for example profiles 8, 5, 0 and 3; while genes in profiles 39 and 49 had opposite effects. They are the predominant expression profiles in our experiment , and consist of genes with the tendencies consistent with or opposite to that occurred during myelosuppression .
In general the ability of HDACi to enhance drug-induced cytotoxicity has been related
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