Researchers have found the key protein of leukemia

According to studies on recombinant mouse proteins, scientists have found that regulatory protein ENL can promote the occurrence of leukemia. This has deepened the academic understanding of transcriptional regulation and suggests a potential leukemia therapy.

The cause of blood tumors is usually chromosome translocation, resulting in two proteins connected to the formation of fusion protein, and ultimately causing disease. Recombinant protein in regulatory protein mixed lineage leukemia (MLL) is also commonly found in invasive childhood leukemia and is associated with poor prognosis. Therefore, it is necessary to develop a leukemia treatment strategy based on MLL rearranged (MLL-r) fusion protein. In the journal Nature, Erb et al. and He et al., point out that ENL protein is a key factor in the survival of MLL-r cells in leukemia. Erb et al. and Wan et al. have shown that this "read" ability of ENL to acetylated histones is critical to induction of MLL-r leukemia.

Erb et al. and Wan et al. found another complementary mechanism for SEC and DotCom stability. They found that the inactivation of ENL weakened the function of SEC and DotCom in MLL-r cells. The ability of ENL to bind to SEC and DotCom suggests a model that recognizes the acetylated H3 through the YEATS domain, enhancing the stability of the SEC and DotCom complexes with DNA binding and regulating the activity of the genomic abnormalities.

Protein ENL is essential for MLL-r leukemia. Some leukemias are found in some of the MLL protein and another part of the protein mixture of protein. The second protein is usually part of the SEC (super elongation complex) protein complex or the DotCom (DOT1L-containing complex). Both of these protein complexes regulate gene transcription procedures in MLL-r leukemia (complete and partially fused SEC / DotCom complexes). The ENL protein binds to two complexes, while the complex is fused to the MLL in the cell. ENL interacts with the fused SEC / DotCom and interacts with the fused SEC / DotCom. ENL contains a YEATS domain that recognizes a specific acetyl (Ac) on histone H3. Erb et al. and Wan et al. demonstrated that the YEATS domain of the ENL protein helps to stabilize the binding of SEC and DotCom to DNA and promote gene expression that drives leukemia.

This new model suggests a possibility that drugs such as small molecule inhibitors targeting the ENL YEATS domain can selectively kill leukemia MLL-r cells. Other cell types appear to be able to tolerate ENL loss to a large extent, but the SEC, DotCom and ENL are expressed in a variety of cells, so it is important to understand this tolerance when developing such drugs on the difference.

The effect of these combination therapies suggests that multiple histone-modified signals act together to form a specific epigenetic state of MLL-r leukemia. Thus, long-targeted therapy is more effective and can reduce the emergence of drug resistance - which is one of the risks of single drug therapy. Thus, Erb et al. and Wan et al.'s findings on ENL not only deepen our understanding of how cells integrate transcription-related signals, but also provide new insights into the treatment of complex diseases. By the way, Flarebio offers high-quality recombinant proteins like recombinant ECE1 at competitive prices.