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Monitoring response and resistance to the novel arsenical darinaparsin in an AML patient

ABSTRACT: A patient diagnosed with AML with inversion of chromosome 3 inv(3)(q21q26.2) was treated with the organic arsenical darinaparsin on an experimental protocol. The patient underwent two treatment cycles. During the first, a stabilization of WBC counts was noted along with a marked improvement in subjective well-being. During the second cycle, the patient's WBC counts continued to increase suggesting the emergence of resistance. RNA was isolated from PBMCs before each cycle and after 48 hours of darinaparsin treatment in each cycle. Gene expression changes were determined by Agilent 8x60K array.

ORGANISM(S): Homo sapiens

PROVIDER: GSE43455 | GEO | 2014/01/01

SECONDARY ACCESSION(S): PRJNA186447

REPOSITORIES: GEO

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Project description:The counts of total white blood cells (WBCs) and WBC subsets are well-established diagnostic factors for various diseases. It has been shown that variations in WBC counts are significantly controlled by individuals’ genetics in swine. However, despite detection of quantitative trait loci (QTLs) for these phenotypes, little is known on the molecular basis underlying their variations. Our aim was to study gene profiling variations according to variations in WBC counts and to connect results with available QTL mapping. Whole blood transcriptome of animals contrasted for levels of WBC counts were compared. A pig generic microarray enriched in immunity-related genes was used. 378 probes representing 334 genes were found significantly differentially expressed between high- and low-count WBC groups. 65 genes were associated with hematological system development and function. 336 probes could be mapped on all autosomes and the X chromosome, and 59 transcripts fell within 28 QTLs reported to affect the counts of WBC and WBC subsets. By combining probe mapping results and biological functions, 6 genes (CDKN2A, TCIRG1, SIPA1, RGL2, FLT1 and CFLAR) were found as putative relevant positional candidate genes for the WBC traits. Genetic linkage experiments are warranted to validate these candidate genes, and further investigating a possible pleiotropic effect of these genes could contribute to elucidate molecular mechanisms involved in WBC development. differentially expressed genes or transccripts between high- and low-count white blood cells groups The dual channel microarray experiments were carried out using a common reference hybridization design. In this study the reference RNA sample was prepared by pooling of total RNAs from different porcine tissues. The test samples were RNA samples isolated from total porcine blood. According to the total white blood cells count, 18 animals were selected from the edges of the distribution, named high-count group (HC, 9 animals) and low-count group (LC, 9 animals).

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Monitoring response and resistance to the novel arsenical darinaparsin in an AML patient

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