One step closer to understanding T-cell leukemia

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T-cell leukemia is rare blood cancer in the own immune system. T-cell acute lymphoblastic leukemia, a special form of T-cell leukemia, was investigated by Belgian researchers with striking findings.

In a recently conducted patient study, a R98S mutation in ribosomal protein L10 recurred in 8% of children with T-cell acute lymphoblastic leukemia.

This protein plays an important role in the JAK-STAT signaling pathway which transmits chemical signals from the extracellular matrix into the nucleus and finally influences the transcription of DNA and expression of genes.

JAK-STAT signaling pathway
JAK-STAT signaling pathway.
(By Peter Znamenkiy – Own work, Public Domain,
The three main components in the JAK-STAT pathway are the cell surface receptor (JAnus Kinase) and two Signal Transducer and Activator of Transcription (STAT) proteins.

The group of Kim de Keersmaecker from KU Leuven in Belgium investigated this mutation in greater detail by creating a customized gene knock-in mouse model with PolyGene.

In the transgenic R98S mouse, several proteins in the oncogenic JAK-STAT pathway are overexpressed, and increased sensitivity to clinically used JAK-STAT inhibitors like pimozide was observed. These findings link a ribosomal mutation to the JAK-STAT pathway, adding to the rapidly expanding repertoire of oncogenic mechanisms exploited by ribosomal defects in cancer. Moreover, the JAK-STAT cascade was identified as an attractive therapeutic target in RPL10 R98S positive T-cell acute lymphoblastic leukemia.

Interested in knock-in services for your gene(s) of interest? PolyGene offers:

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