dac  (MedChemExpress)

Journal: bioRxiv

Article Title: Integrating functional genomics and proteomics identifies Folate Carrier SLC19A1 as a predictor of pralatrexate sensitivity in T-cell lymphoma

doi: 10.1101/2025.10.08.681217

Figure Lengend Snippet: Volcano plots of phenotype scores and P values from genome-wide CRISPR interference screens under treatment with ( A ) pralatrexate, ( C ) bortezomib, ( D ) gemcitabine, ( E ) romidepsin, and ( F ) oxaliplatin. Orange points denote gene knockdowns with false discovery rate (FDR) below 10%, calculated from comparison with ‘pseudogene’ controls from non-targeting guide RNAs (gray; Methods); this threshold corresponds to Mann Whitney P values <0.05 (noting that FDR is not type 1 error). B . Effect of SLC19A1 knockdown on pralatrexate resistance. Pralatrexate dose response was measured in SU-DHL-1 cells expressing dCas9-KRAB, either untransformed, transformed with a non-targeting guide RNA, or transformed with a guide RNA targeting SLC19A1. Error bars show the standard deviation of four replicate measurements. At a physiologically relevant pralatrexate concentration (60nM, based on human pharmacokinetic studies) SLC19A1 knockdown abolished pralatrexate response compared with non-targeting control ( P = 0.00002, Student’s t-test).

Article Snippet: Five therapies used in the treatment of T-cell Lymphoma were purchased from MedChemExpress; romidepsin (Catalog number: HY15149, pralatrexate (Catalog number: HY-10466), bortezomib (Catalog Number: HY-10227), gemcitabine (Catalog Number: HY-17026), oxaliplatin (Catalog number: HY-17371).

Techniques: Genome Wide, CRISPR, Comparison, MANN-WHITNEY, Knockdown, Expressing, Transformation Assay, Standard Deviation, Concentration Assay, Control

Journal: bioRxiv

Article Title: Integrating functional genomics and proteomics identifies Folate Carrier SLC19A1 as a predictor of pralatrexate sensitivity in T-cell lymphoma

doi: 10.1101/2025.10.08.681217

Figure Lengend Snippet: A. Example dose-response measurements of T– and NK-cell lymphoma cultures treated with pralatrexate for 72 hours. Cell viability was measured by luminescence (CellTiter-Glo) relative to untreated controls. Replicates included two independently propagated cultures, assayed on different plates across different weeks, yielding 3-4 replicates for each of 30 lymphoma cultures. B. Normalized drug sensitivities of 30 lymphoma cultures to 5 therapies used in the second-line treatment of PTCL. Sensitivities were quantified as the area over the dose-response curve (AOC), up to a clinically relevant maximum concentration (0.9 μM romidepsin , 0.06 μM pralatrexate , 0.8 μM bortezomib , 0.1 μM gemcitabine , and 4 μM oxaliplatin ). White asterisks mark cultures in the top quartile of sensitivity to each therapy. C. Heatmap indicating which lymphoma cultures are in the top quartile of sensitivity to one or more drugs.

Article Snippet: Five therapies used in the treatment of T-cell Lymphoma were purchased from MedChemExpress; romidepsin (Catalog number: HY15149, pralatrexate (Catalog number: HY-10466), bortezomib (Catalog Number: HY-10227), gemcitabine (Catalog Number: HY-17026), oxaliplatin (Catalog number: HY-17371).

Techniques: Concentration Assay