PYCR1 inhibition in bone marrow stromal cells enhances bortezomib sensitivity in multiple myeloma cells by altering their metabolism

Despite significant advancements, multiple myeloma (MM) remains incurable, largely due to drug resistance. Our previous research has demonstrated that proline metabolism plays a role in MM progression and that inhibiting PYCR1, the final enzyme in proline synthesis, enhances bortezomib sensitivity in MM cells. Given the high expression of PYCR1 in bone marrow stromal cells (BMSC), we sought to investigate the effects of PYCR1 inhibition in BMSC and its indirect influence on MM cell metabolism and viability. Culturing MM cells in conditioned medium (CM) of PYCR1-silenced BMSC significantly impaired oxidative phosphorylation and sensitized MM cells to bortezomib. Analysis of the CM secretome revealed a reduction in activin A release. Proline and activin A supplementation were able to counteract MM sensitivity to bortezomib. Combination therapy of the PYCR1 inhibitor pargyline and bortezomib reduced tumour load in a 3D model and reduced serum activin A levels in 5TGM1-bearing mice. This st..., Data output from in vitro experiments. Read outs were extracted, placed in excel and statistical analysis was done with graphpad prism., , # Data from: PYCR1 inhibition in bone marrow stromal cells enhances bortezomib sensitivity in multiple myeloma cells by altering their metabolism

[https://doi.org/10.5061/dryad.547d7wmk2](https://doi.org/10.5061/dryad.547d7wmk2)

## Description of the data and file structure

Data collected for the in vitro experiments have been collected in an Excel file. Every tab represents a figure panel, for example, \"S2A\" means data collected for supplementary figure 2, panel A. Tabs exist for figures 1-5 and supplementary figure S1-3.

### Files and variables

#### File: Data_Paper_PYCR1_update.xlsx

**Description:** In vitro & In vivo data

##### Variables

* 1A: Normalized mRNA expression data of microarray data Heidelberg-Montpellier cohort (ArrayExpress public database under accession number E-MTAB-362)
* 1E, S1B: Relative pixel intensity of density bands Western Blot
* 1D, 4C, S1A, S2A: Relative RNA expression
* 2A, 2C, S3A, S3C: oxygen consumption rate (OCR) in pmol/min/1000 cells
* 2B, S3..., ,