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| Status |
Public on Jul 08, 2020 |
| Title |
Gene expression profiles of TEL-AML1 acute lymphoblastic leukaemia blasts retrieved from central nervous system and spleen |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Purpose: To investigate metabolic adaptation of leukaemia in two different microenvironments: central nervous system and spleen
Methods: The REH (TEL-AML1) cell line representing a standard-risk subtype was used. Cells were transplanted into immunodeficient mice. CNS tropism was demonstrated and ALL blasts invaded the leptomeninges in a timeframe ranging from 4 to 5 weeks. At experimental endpoint, blasts were retrieved from the CNS and periphery (spleen), and their gene expression profiles were compared using RNA-sequencing. The raw reads were pre-processed with Cutadapt v.1.5 and Sickle v.0.940 software. Transcript expression quantification was performed using Kallisto v.0.42.4 software against combined human and mouse transcriptomes, Ensembl GRCh38.79 and GRCm38.78, respectively. Read counts related to human transcripts were collected, rounded, and summarized into gene specific read counts. Gene-based differential expression analysis was done with DESeq2 R-package. Preprocessed RNA expression data from RNA sequencing was analysed further using single sample gene set enrichment analysis (ssGSEA).
Results: The human REH cells’ gene expression profiles clustered according to site of colonization in the transplanted mice; CNS versus spleen. Top differentially expressed genes were associated with cellular metabolism or stress responses. ssGSEA analysis identified positive correlation of lipid and lipoprotein metabolism signatures in CNS-derived cells, with particular propensity towards fatty acid synthesis. On the other hand, oxidative phosphorylation processes, linked to fatty acid degradation, were negatively correlated with CNS involvement and enriched in REH cells from the spleen of transplanted mice.
Conclusions: We demonstrate that leukaemic cells undergo widespread dynamic rewiring of metabolism when switching from bone marrow to CNS microenvironments, resulting in altered therapeutic vulnerabilities. We observed a strong fatty-acid synthesis signature in CNS leukaemia, highlighting Stearoyl-CoA desaturase (SCD1) as a key player.
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| Overall design |
Gene Expression profiles of human leukaemic cells retrieved from CNS and spleen after cell transplantaton into immunodeficient mice, were generated by RNAseq using Illumina NextSeq 500 sequencer.
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| Contributor(s) |
Olivares O, Cousins A, Herzyk P, Markert EK, Gottlieb E, Halsey C |
| Citation(s) |
33479702, 36289348 |
| |
| Submission date |
Jul 30, 2019 |
| Last update date |
Nov 03, 2022 |
| Contact name |
Pawel Herzyk |
| E-mail(s) |
pawel.herzyk@glasgow.ac.uk
|
| Phone |
00441413303180
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| Organization name |
University of Glasgow
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| Department |
College of Medical, Veterinary and Life Sciences
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| Lab |
Glasgow Polyomics
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| Street address |
Wolfson Wohl Cancer Research Centre, Garscube Estate
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| City |
Bearsden |
| ZIP/Postal code |
G61 1QH |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (5)
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| This SubSeries is part of SuperSeries: |
| GSE135115 |
Gene expression profiles of MLL-AF4 and TEL-AML1 acute lymphoblastic leukaemia blasts retrieved from central nervous system and spleen |
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| Relations |
| BioProject |
PRJNA557460 |
| SRA |
SRP216846 |
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