Nature Subsidiary: Scientists have built a supergene map to fight this dangerous leukemia
Release date: 2017-07-06
On July 3, Nature's publication Nature Genetics published the first largest genome sequencing result for a malignant childhood blood tumor, T-type acute lymphoblastic leukemia (T-ALL). Scientists from research institutions such as the Children's Hospital of St. Jude and the Children's Oncology Research Group conducted genome sequencing of hundreds of T-ALL patients and performed a series of complex analyses to construct an unprecedented genetic map.
Charles Mullighan and Yu Liu
On July 3, Nature's publication Nature Genetics published the first largest genome sequencing result for a malignant childhood blood tumor, T-type acute lymphoblastic leukemia (T-ALL). Scientists from research institutions such as the Children's Hospital of St. Jude and the Children's Oncology Research Group conducted genome sequencing of hundreds of T-ALL patients and performed a series of complex analyses to construct an unprecedented genetic map.
This map provides more therapeutic information for T-type acute lymphoblastic leukemia, and has unearthed many previously undiscovered mutant genes, which contribute to the construction of animal models, the development of new drugs, and the analysis of new pathogenic mechanisms.
The study was led by Charles Mullighan, Professor of Pathology at St. Jude Children's Hospital, Jinghui Zhang, Head of Computational Biology, Children's Hospital, and Stephen Hunger, Children's Hospital of Philadelphia.
Type T acute lymphoblastic leukemia
Acute lymphocytic leukemia is the most common childhood cancer, and approximately 90% of children with ALL can be cured, but there is a probability of recurrence. Among them, T-ALL occupies a 15% ratio, and T cells in the immune system lose their ability to mature and function due to multiple mutations. The mutated T cells accumulate in the body and replace the normal cells.
In general, the Notch signaling pathway, the T cell transcription factor, and the INK4/ARF tumor suppressor gene are important markers for T-ALL, but large-scale genome sequencing work on T-ALL has never been performed.
Construct a genetic map and mine up to 106 driving genes
The research team recruited 264 children and young patients for genome testing. In the first article, Yu Liu, a postdoctoral fellow in the Jinghui Zhang group, conducted a complex analysis of various genomic data. They screened a total of 106 disease-causing genes that cause T cell dysfunction and lead to cancer. Among them, half of the mutant genes are newly discovered and associated with T-ALL.
The researchers analyzed cancerous T cells and compared them with T cells that remained normal for treatment, providing valuable clues to the mechanism by which specific treatments successfully block specific carcinogenic mutations.
Cancer is driven by mutated genes, and proteins/enzymes expressed by these genes are involved in important signaling pathways. Although cancer is likely to be triggered by the initial genetic mutation, this mutation site triggers a series of other mutations that exacerbate the onset and progression of cancer. New genomic analysis confirmed that T-ALL is driven by mutations in known signaling pathways, including JAK-STAT, Ras, and PTEN-PI3K. In addition to these drive mutations, there are more known mutations in the pathway leading to disease.
Charles Mullighan and Jinghui Zhang
“This is the first comprehensive, systematic, large-scale analysis that reveals many biologically significant mutations that are expected to become drug targets, and has great clinical implications,†Mullighan said. “Leukemia is usually caused by multiple genetic mutations. Most previous studies did not get enough genomic data to screen for mutations and look for associations between them. Now we have dig into many previously undiscovered mutation sites."
Reference material
" First large-scale genomic analysis of key acute leukemia will likely yield new therapies "
Source: Bio-Exploration (micro-signal biodiscover)
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