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Scientists offer new treatment for a fatal subtype of leukaemia

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Posted July 28, 2015

Leukaemia is a group of cancers that affect blood of those who suffer from this disease. It starts in the bone marrow and result in high numbers of abnormal white blood cells. In such industrialized countries like Switzerland leukaemia represents the most frequent type of cancer in children. Now scientists in the University of Zurich together with a team of international researchers have succeeded in decoding a rare but always fatal subtype of this disease and now are creating new treatment options.

Acute lymphoblastic leukaemia represents the most frequent type of cancer in children in industrialized countries. Some subtypes of it are always fatal, but studies like this provide hope that it may be cured in the future. Image credit: Furfur via Wikimedia, CC BY-SA 2.5

Acute lymphoblastic leukaemia represents the most frequent type of cancer in children in industrialized countries. Some subtypes of it are always fatal, but studies like this provide hope that it may be cured in the future. Image credit: Furfur via Wikimedia, CC BY-SA 2.5

This fatal subtype of acute lymphoblastic leukaemia usually develops between the age of two and three. This type of leukaemia has several subtypes, which are different because of certain changes in the genetic material of the leukaemia cells. Now teams of highly skilled scientists have managed to identify the genome of a currently incurable subtype of acute lymphoblastic leukaemia. This subtype features incorrect fusion of two genes, called TCF3 and HLF.

Such fusion is the reason why this subtype of acute lymphoblastic leukaemia is always fatal – this change in the genetic code confers resistance to all current cancer treatments. Furthermore, scientists now have also discovered that in addition to this incorrect fusion of genes other areas in DNA endure changes as well.

In the leukaemia cells that were studied in the research, defective genes that control the development of highly specific blood defence cells, so-called B-lymphocytes, and promote cell growth were altered.  The incorrect fusion of TCF3 and HLF genes triggers a previously underestimated reprograming of the leukaemia cells to a very early, stem-cell-like developmental stage. The worst part about this condition is that it cannot be detected by current diagnostic tests. Scientists described it as a wolf hiding in sheep’s clothing – cancer sort of is hidden in early stages from current medical technologies.

As often is the case, scientists used mouse models. Researchers developed a humanized mouse model that enables researchers to explore leukaemia in conditions that are very similar to the situations encountered in humans. This effort was made in order to create personalized treatments and research possible targets for drug therapies. Because human leukaemia cells growing in the mouse retain the crucial genetic changes, mouse models constitute a great opportunity to examine new courses of therapy in a manner that is much more patient-oriented. Such basis for experiments already served its purpose pretty well – team of researchers were able to test hundreds of novel drugs.

Some of these drugs are still undergoing further clinical development and are not used in hospitals. However, some of the drugs tested displayed a very positive effect. For example, Venetoclax, which specifically targets the protein BCL2 relevant for the programmed cell death and already worked for other cancer strains, showed a great potential in treating acute lymphoblastic leukaemia as well in these experiments.

This drug triggered a significant decline in the acute lymphoblastic leukaemia in mouse models. Furthermore, decline in the disease was followed by lengthy phases without any signs of the cancer if administered with conventional chemotherapy for leukaemia. Jean-Pierre Bourquin, lead author of the study, said – “further studies are now needed to test how the results of our study might be used for therapeutic possibilities. Our work just goes to show the great potential of coordinated, interdisciplinary research approaches involving cutting-edge technological possibilities for cancer research”.

Studies like this are extremely needed and provide hope that science is getting closer and closer to solving one of the greatest health problems of 21st century. All cancer types are getting needed attention from scientists, but those types of cancer than affect children the most should be cured as soon as possible. However, it will still take a lot of time for studies like this to bring positive results to patients waiting in hospitals.

Source: UZH

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