Innovation Pharmaceuticals Inc (IPIX)

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Perhaps this will shed a little more light

KEVETRIN DAMPENS MYC EXPRESSION AND CELLULAR METABOLISM IN ACUTE MYELOID LEUKEMIA

Results:
The TP53-wt cell line showed a sensibility only at the highest drug concentration with a decreased cell viability and a significant increase in Annexin V+ cells (54.95 ± 5.63 % vs 12.53 ± 6.15 % of the CTRL). KASUMI-1 cell line showed a significant dose- and time-dependent cell growth inhibition and apoptosis increase with 79.70 ± 4.57 % of Annexin V+ cells at 60 µg/ml (vs 13.18 ± 0.80 % of the CTRL). Short-term (6 h) kevetrin treatment induced few alterations of the overall transcriptional program, with a differential expression of FOXK2 and STAT5A, which were 2-fold downregulated in KASUMI-1. Moreover, metallothionein 1 and 2 were upregulated by kevetrin exposure in both cell lines. After prolonged kevetrin treatment (48 h) we found 1024 upregulated and 1563 downregulated genes in MOLM-13 cell line, whereas KASUMI-1 showed increased expression of 325 and decreased levels of 1535 genes. Kevetrin exposure targeted also a common core transcriptional program in the selected models, including 162 upregulated and 812 downregulated genes. Enrichment analysis of the core transcripts showed that upregulated genes were mainly involved in transcription, nucleosome assembly and telomere organization, apoptosis, autophagy, NF-kB pathway and MAPK activity. Downregulated genes were mostly involved in cell cycle, DNA repair, biosynthetic processes, bioenergetics, translation, telomere maintenance and splicing. Among the most relevant genes we found critical regulators of myelopoiesis and leukemogenesis, such as MYC, MYB, BCL11A and EZH1, leukemia-related genes involved in unfolded protein response (JUN), signaling, glycolysis (HK2), DNA methylation (IDH2) and the tumor suppressor gene TP53. GSEA of microarray data showed that kevetrin-treated cells shared the downregulation of glycolysis, DNA repair, unfolded protein response and MYC target gene sets (Figure).

https://journals.lww.com/hemasphere/Pages/articleviewer.aspx?year=2019&issue=06001&article=01570&type=Fulltext

Message in reply to:
Found Transcriptional used in this wikipedia link discussing cell regulation. Hope we hear more on this.

https://en.wikipedia.org/wiki/Transcriptional_regulation