Publications by authors named "Bryann Pardieu"
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 PDFSuper Enhancers (SEs) are clusters of regulatory elements associated with cell identity and disease. However, whether these elements are induced by oncogenes and can regulate gene modules cooperating for cancer cell transformation or maintenance remains elusive. To address this question, we conducted a genome-wide CRISPRi-based screening of SEs in ETO2-GLIS2 acute megakaryoblastic leukemia.
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- Cancer cells adapt to stress, creating weaknesses that can be targeted; a study found that VCP, a stress-related protein, is particularly vulnerable in acute myeloid leukemia (AML).
- The research showed that AML is the most sensitive cancer type to VCP inhibition, validated through various models and techniques.
- A new VCP inhibitor, CB-5339, was developed and shown to effectively work with DNA-damaging drugs like anthracyclines, supporting its potential for clinical testing in AML treatment.
Article 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.
Article Synopsis
- Local adaptation helps organisms survive in specific environments by developing useful traits, but fast changes in the environment can sometimes create problems instead of solutions.
- Researchers studied how cancer cells, specifically acute myeloid leukemia (AML), change when exposed to different treatments, revealing a complicated relationship between drug resistance and sensitivity.
- They discovered that certain genetic pathways in these cells can make them resistant to one type of treatment while making them more vulnerable to another, which could help develop better cancer therapies that target this weakness.