How Fusion Genes Lead To Leukemia

Researchers in Japan have identified a recurring fusion gene associated with poor prognosis in pediatric T-cell lymphoblastic leukemia.

AsianScientist (Dec. 21, 2017) – In a study published in Nature Genetics, researchers at the University of Tokyo, Japan have identified recurrent fusion genes linked to a subtype of childhood leukemia.

Fusion genes refer to abnormal genetic material formed from the combination of two or more separate genes. Such anomalies in patients are known to cause cancers such as leukemia. However, the specific type of fusion genes differs among leukemia patients and has an impact on their prognosis.

In the present study, the team of scientists led by Associate Professor Junko Takita, Assistant Professor Masafumi Seki and Dr. Shunsuke Kimura at the Department of Pediatrics at the University of Tokyo Hospital obtained comprehensive profiles of genetic abnormalities, fusion genes and structural variants in the genomes of 123 pediatric T-cell acute lymphoblastic leukemia (T-ALL) patients using next-generation sequencing.

The team identified recurrent fusion genes containing a segment of a gene called SPI1, which is related to extremely poor prognosis in four percent of pediatric T-ALL patients. SPI1 is a transcription factor, a type of protein responsible for gene regulation that is instrumental in the differentiation of blood cells. The diminished expression of SPI1 in immune cells known as T-cells is thought to play an important role in differentiation.

The researchers demonstrated that overexpression of SPI1 fusion genes blocks the differentiation and proliferation of T-cells, thereby highlighting the possibility that excess SPI1 promotes the development of leukemia. Furthermore, by profiling the gene expression and examining the molecular features of pediatric T-ALL, the researchers revealed that the disease could be divided into five clusters, each characterized by specific gene expression, genetic abnormalities and clinical features.

“There had not been any reports so far on molecular markers related to pediatric T-ALL with a poor prognosis,” said Takita. “Cases with SPI1 fusion genes show a dismal prognosis, likely requiring a higher risk classification and more intensive treatment. Targeted therapy employing highly accurate molecular diagnosis could prove effective in treating the disease in the future.”

The article can be found at: Seki et al. (2017) Recurrent SPI1 (PU.1) Fusions in High-Risk Pediatric T Cell Acute Lymphoblastic Leukemia.


Source: University of Tokyo; Photo: Shutterstock.
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