A Major Vulnerability of Childhood Leukemia Discovered!

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Childhood leukemia is a severe case to be treated. Over the years, better treatments have come forth but a few particular types of this cancer remain incurable, such as the mixed lineage leukemia, with the death rate of 50%.

But now recent research is making an appearance in an issue in journal PNAS, reveals that a protein called LEDGF/p75 is regulated by a molecular modification that alters its electric charge, called phosphorylation. LEDGF/p75 plays role in the regulation of gene expression by attaching other proteins to particular epigenetic spots on chromatin. This function is hindered by two diseases, mixed lineage leukemia and HIV. There is not much known about LEDGF/p75 interactions with its binding partners in this biological regulation which limited better way of targeting LEDGF/p75 interactions in these diseases.

However, recently in an extensive structural analysis, researchers have discovered a structurally conserved specific binding mood that is attributed to all LEDGF/p75 binders, necessary for the interaction to take place. This discovery opened ways for the researchers to investigate other previously unknown interactions that take place between LEDGF/p75 and other transcriptional regulatory factors. These factors are known well in the medical community and include important regulators like Mediator complex. This revealed that LEDGF/p75 interacts with a greater number of factors than was thought. The binding is found to be modulated by phosphorylation by an enzyme (Casein Kinase 2).

With the help of this breakthrough, researchers developed new therapeutic strategies. The team demonstrated the concept by successfully eliminating phosphorylation sites present in MLL1, one LEDGF/p75 binding partner. It reduced the ability of leukemic cells to stay in a cancerous state. The interaction is a requirement for cancers cells only and do not affect the normal functioning of blood cells.

In inhibiting the phosphorylation that makes the binding of LEDGF/p75 and MLL1 possible, new therapeutic strategies can be initiated against mixed lineage leukemia. Due to its adherence only to a cancer cell, more effective therapies will hopefully come forth