Jmjd3 Drives Immature T-Cell Lymphoblastic Leukemia

T-ALL represents a highly aggressive haematological malignancy, characterized by an unmet clinical need, particularly in refractory patients or those resistant to standard treatments. Dr Tim Pieters, PhD at Ghent University describes his investigative approach, utilising mouse models that overexpress specific oncogenes to delve into the intricate biology of immature T-ALL.

His focus centres on unravelling the role of Jmjd3, a demethylase with a D-metallase domain, in tumour initiation. This exploration involves the overexpression of Jmjd3 within the hematopoietic system, driving the development of a distinctly immature subtype of T-ALL.

To dissect the molecular mechanisms at play, single-cell RNA sequencing on control spleens and splenic tumours within the mouse model was conducted. This analysis revealed the presence of genes associated with very immature T-ALL, alongside more mature T-cell markers such as CD3, CD4, and CD8.

Further scrutiny identified elevated expression of the SPI-1 gene in the tumour fraction of the single-cell RNA sequencing dataset. This discovery was corroborated through proteomics analysis. Ongoing experiments are underway to elucidate the precise molecular mechanisms underlying these findings.

Reference:

Pieters T, ASH2023. #4341

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