Altered growth and molecular features of Jurkat cells after introduction of the BCR-ABL1 p190 gene fusion

ABSTRACT: The Philadelphia Chromosome is the result of a balanced reciprocal translocation be-tween the long arms of chromosomes 9 and 22, resulting in the fusion gene BCR-ABL1. Despite its being a hallmark of acute lymphocytic leukemia (ALL), acute myelogenous leukemia (AML) and mixed-phenotype acute leukemia, still comparatively little is known about effects that can be directly attributed to its presence in cancer cells. In order to study this question, we have created and characterised a Jurkat cell line with such an alteration, using a CRISPR/Cas9 based approach. The BCR-ABL1 p190 carrying cells we created showed increased proliferation as well as elevated sensitivity towards tyrosine kinase inhibitors as compared to unaltered Jurkat cells. By comparing gene expression, DNA-methylation and protein expression data, generated by NGS and mass spectrometry analyses, we were able to identify a number of pathways as well as individual proteins that show specific responses to the presence of BCR-ABL1 p190. Among the deregulated proteins we found known cancer proteins such as the tumor suppressors ASS1 and ABI3, which were downregulated in our model, or the specifically upregulated TRBC1. With an almost fivefold expression DPYSL5 showed the highest upregulation and PLEK was the protein with the strongest decrease (8.8 fold). Particularly noteworthy is the downregulation of CYP51A1 which is known to confer TKI-resistance under normal circumstances and is therefore directly in line with the increased TKI sensitivity of our BCR-ABL1 p190 positive cells. Also of interest is SPART, whose expression in our model was increased despite strong hypermethylation and it can be assumed that this paradoxical regulation might be directly attributable to the Philadelphia Chromosome.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Suspension Culture

SUBMITTER: Thomas Sura  

LAB HEAD: Elke Hammer

PROVIDER: PXD071195 | Pride | 2026-02-23

REPOSITORIES: Pride