Publications by authors named "Justine Pasanisi"
Functional precision medicine in AML often relies on short-term in vitro drug sensitivity screening (DSS) of primary patient cells in standard culture conditions. We designed a niche-like DSS assay combining physiologic hypoxia (O 3%) and mesenchymal stromal cell (MSC) co-culture with multiparameter flow cytometry to enumerate lymphocytes and differentiating (CD11/CD14/CD15+) or leukemic stem cell (LSC)-enriched (GPR56+) cells within the leukemic bulk. After functional validation of GPR56 expression as a surrogate for LSC enrichment, the assay identified three patterns of response, including cytotoxicity on blasts sparing LSCs, induction of differentiation, and selective impairment of LSCs.
View Article and Find Full Text PDFBy querying metabolic pathways associated with leukemic stemness and survival in multiple AML datasets, we nominated SLC7A11 encoding the xCT cystine importer as a putative AML dependency. Genetic and chemical inhibition of SLC7A11 impaired the viability and clonogenic capacity of AML cell lines in a cysteine-dependent manner. Sulfasalazine, a broadly available drug with xCT inhibitory activity, had anti-leukemic activity against primary AML samples in ex vivo cultures.
View Article and Find Full Text PDFArticle Synopsis
- Researchers are studying how metabolic changes, particularly in amino acid pathways linked to the folate cycle, affect the effectiveness of cancer treatments in acute myeloid leukemia (AML).
- They found that lower levels of folate and a specific gene variant affecting the MTHFR enzyme can lead to resistance against certain cancer therapies targeting MYC in both lab models and patient samples.
- Supplementing with CH-THF, a product of the MTHFR enzyme, can potentially overcome this resistance, suggesting that assessing individual folate cycle status may help identify patients who could benefit most from MYC-targeting treatments.
Intra-tumor heterogeneity portends poor outcome in many cancers. In AML, a higher number of drivers worsens prognosis. The Shannon Index is a robust metric of clonal heterogeneity that accounts for the number of clones, but also their relative abundance.
View Article and Find Full Text PDFBromodomain and Extra-Terminal inhibitors (BETi) such as OTX015 are active in Acute Myeloid Leukaemias (AML). Their activity on Leukemic Stem Cells (LSCs) is less documented. We interrogated the anti-LSC activity of OTX015 in a niche-like long-term culture in 26 primary AML samples and validated our findings in vivo.
View Article and Find Full Text PDF