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The proto-oncogene TCL1A deregulates mitotic checkpoint transition and genomic stability in CLL

ABSTRACT: Upregulation of the proto-oncogene TCL1A is causally implicated in various B- and T-cell malignancies. High-level TCL1A correlates with aggressive disease features and inferior clinical outcomes. However, molecular and cell-biological consequences of TCL1A dysregulation are not fully elucidated. To analyze if TCL1A’s oncogenic activity depends on its subcellular localization, we transduced murine hematopoietic stem cells and progenitor cells (HSC/HPC) with three different human TCL1A variants, being wild type, membrane-localized myristoylated (myr) TCL1A, and TCL1A fused to a nuclear localization signal (nls). All three groups developed mostly B-cell leukemias/lymphomas and less frequently CD4/CD8 double-positive or double-negative T-cell leukemia/lymphomas. Mice transplanted with cells expressing nls-hTCL1A had a significantly shorter survival in comparison to mice harboring wt TCL1A. Gene set enrichment analysis of gene expression profiling data from B-cell tumors identified nuclear pathways including DNA repair, cell cycle, and mitotic spindle to be enriched in the nls-hTCL1A over the hTCL1A cohort.

ORGANISM(S): Mus musculus

PROVIDER: GSE192409 | GEO | 2022/11/14

REPOSITORIES: GEO

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The proto-oncogene TCL1A deregulates mitotic checkpoint transition and genomic stability in CLL

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