British scientists have found the medication against most aggressive form of leukemia

Scientists of the Oncology Institute (Great Britain) inform that they have succeeded in finding medication against so called mixed lineage leukemia (MLL).

In recent years medicine has made a great progress in treatment of malignant blood disorders. But this type of the disease exhibits an exceptional resistance to any treatment and is liable to frequent recurrences. In addition, mixed lineage leukemia is considered to be one of the most spread forms of blood cancer. It is the most frequent form of leukemia in children under 2 years old; it is also every tenth episode of blood cancer among adult population.

The reason of mixed lineage leukemia development is an "illegal" molecular rearrangement. In blood cell precursors there are MLL proteins, which serve as genetic switches and in the norm regulate production and differentiation of blood cells. But sometimes it happens to be that several MLL genes are ranged in one line. As a result of information read-out from such DNA there is a fused MLL-protein, where several polypeptide chains are fused into one. It is thought that it this protein monster which launches mixed lineage leukemia.

MLL-proteins interact with DNA and activate the genes of cell division. In case of mutation these proteins do not obey to anything and continue to stimulate the production of new cells with all their strength. Apparently, if it were possible to switch off MLL-proteins, it was the end of cancer development. But to do it, it is necessary to find out how and with which partners MLL work. Scientists inform about another group of proteins called BET, which serve as mediators between MLL and DNA. DNA in the cell is in a complex with chromosomal proteins histones. Activation of this or that gene frequently means its "dearchivation", "unpacking" from histones. BET proteins are something like an adaptor, which connects MLL oncoproteins with histones, and it is MLL which unpack histone bound around genes.

The key moment in the investigation is the fact that it has become possible to find out the attachment means of BET and histones. BET proteins attach to modified histone aminoacids – lysines, to which acetic acid residue is attached. Having learned what BET proteins "like", the researches selected such compound as I-BET151. This reagent adhered to BET at that vey place, where they attached to histones. In such a way, BET stay away from DNA, and MLL joined with them have no possibility to activate cell division. Experiments have proved the efficiency of I-BET151. Cancer cells, treated with this compound, stopped growing and died. The medication increased the survival of mice even with most aggressive form of leukemia: as the authors write, in 40 days after initiation of the treatment course, more than 60% of animals survives, which is more than just a significant number for this disease.

The researches stress on the originality of the proposed medication. A significant part of anticancer preparations either beats the DNA itself, or disable surface receptors of the cancer cell. Several experimental preparations, similar to I-BET151, are aimed at histones bound to DNA, but they have a significantly less specificity. The authors compare I-BET151 with sharpshooter’s bullet, whereas its previous analogues are more like a small short charge.

Clinical studies will be the following step. Scientists are not going to confine themselves to one type of blood cancer; they think that in the same way it is possible to prevent the development of different malignant tumors. 

Adopted from: Eurolab