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Mutations of the LYL1 gene in patients with T‐cell acute lymphoblastic leukemia (59.7)

The lymphoblastic leukemia ‐ 1 (LYL1) gene is a transcription factor believed, when upregulated, to support the formation of T‐cell Acute Lymphoblastic Leukemia (TALL). One possible cause for the upregulation of LYL1 is the presence of mutations, affecting the normal expression, processing or degradation of LYL1. The objective of our study is to identify if there are mutations in the LYL1 gene in patients with TALL, and determine the effect of such mutations on LYL1 expression. RNA, for quantitative PCR, and DNA, for LYL1 sequencing, were extracted from blood and bone marrow samples from twenty TALL patients. Ten samples showed high and intermediate LYL1 expression. Five of them had single nucleotide polymorphism with three of them being non‐silent. LYL1 variants with single or combined mutations were constructed, and their expression, in cultured CHO‐K1 and H441, was measured by western blotting. The LYL1 variants showed significantly increased expression, up to 3.6 fold, compared to the wild type form. Our findings suggest that these mutations may have a role in the expression and processing, or the degradation of LYL1, which not only adds to our understanding of the LYL1 biology, but it may offer one more clue why LYL1 is upregulated in some forms of TALL.