Scientists discover new-type rearrangement mutations of B-ALL

Analysis of B-ALL carcinogenic mutations through recombinant horse proteins is of great significance for prognosis and treatment options. However, it is still not possible to identify the genetic basis of nearly 30% of B-ALL cases.

Researchers at institutions such as St Jude Children's Research Hospital recently conducted a transcriptome analysis of samples from more than a thousand B-ALL patients and found a new class of oncogenic rearrangements. These rearrangements all involve the MEF2D gene, the latter one may combine with at least six other genes (the BCL9 gene is the largest) after rearrangement, resulting in a fusion protein. The average age of patients with these mutations was 14, and the five-year disease-free survival rate was 71.6%. The researchers speculated that 5.3% of the currently unknown B-ALL cases in 30% of those carcinogenic mutations actually showed MEF2D gene rearrangement mutations. The findings are published in the recent issue of journal Nature Communications.

Panobinostat (Farydak) is an inhibitor of histone deacetylase (HDAC) and was approved by FDA in February 2015 for use in combination with bortezomib and dexamethasone to treat multiple myeloma. The researchers found that the HDAC expression levels of B-ALL cancer cells with MEF2D gene rearrangement mutations were significantly higher, and once it was administered panobinostat, its growth will be effectively curbed.

"In the past few decades, we have gained an in-depth understanding of the genetic changes that have led to ALL," said Dr. Stephen P. Hunger, Ph.D., author of The Children's Hospital of Philadelphia. "However, this study shows that we are still discovering new-type ALL subtypes. Gene mutations that occur in these ALL cancer cells will provide important information about therapeutic efficacy and accurate medical planning."

In addition to MEF2D gene, the researchers also found 20 patients with ZNF384 gene rearrangement mutations. ZNF384 protein is also a transcription factor. Among them, ZNF384 can recombine with other six genes to produce fusion protein. Analysis showed that B-ALL cancer cells carrying MEF2D and ZNF384 gene rearrangement mutations had a unique gene expression pattern. This suggests that the above fusion proteins are likely to be the key factors leading to cancer.

In the colony-forming experiments, the researchers also found that the MEF2D-BCL9 fusion protein could significantly enhance the proliferation of mouse lineage negative bone marrow cells by viral vectors, while the normal MEF2D or BCL9 protein did not.

"This suggests that the formation of MEF2D fusion proteins is a critical step in the transformation of leukocytes with limited longevity into infinitely proliferating leukemic cancer cells," said Dr. Charles G. Mullighan. Flarebio provides you with good-quality recombinant proteins such as recombinant TLR2 at great prices.