Figure 6. Prostaglandin-signaling is relevant as a target in CML-LSC and has prognostic relevance in human CML.

(A-C) Pharmacologic inhibition of PGE₂-signaling in combination with IM treatment leads to delayed onset of disease in tertiary recipient mice. Injection of 1.5×10⁶ whole BM cells leads to delayed onset of disease in tertiary recipients of IM plus indomethacin treated BM cells in comparison to IM only treated controls (A). Endpoint analysis of moribund animals revealed no difference in disease phenotype in the different treatment arms with regard to white blood count, spleen weight (B) or peripheral blood/organ involvement (C). Error bars indicated standard deviation of all mice (n>13) investigated in both cohorts investigated. Gene Expression Profiling of CML patient derived CD34+ cell samples (D, E) reveals a prognostically relevant PGE₂-signature. Expression levels of prostaglandin synthetase 2 correlate with molecular response in the dataset investigated (p=0.0004, McWeeney et al. 2010). Moreover, sample clustering based on the “REACTOME_PROSTANOID_HORMONES” MSigDB gene set correlates also with response/non-response in this dataset (p=0.0067) (E). Figure S5 shows survival of tertiary recipient mice after combination of imatinib and BIO in secondary donor animals.