Leukemia, also known as blood cancer, is a kind of malignant disease concerning the hematopoietic tissue, in which a large number of leukemic cells would proliferate unlimitedly, then entering peripheral blood and badly inhibit normal cells production. Despite its longstanding infamous name of being the top killer of youngsters, the pathogenic root cause of the disease is still unknown. Scientists from European Molecular Biology Laboratory (EMBL), European Bioinformatics Institute (EBI), Harvard University (USA) and Lund University (Sweden) recently discovered that, when a mutant gene from the leukemia patient was introduced into the mouse by genetic engineering method, this introducing gene would trigger the congenital genetic program, which led to the uncontrolled proliferation of leukemic cells and thereby brought the acute leukemia. This discovery is a great breakthrough in treating leukemia, and the relevant paper has been published on “Cancer Cell’ (April 8).

As is generally known, blood cells are differentiated from the very small number of multipotent stem cells in vivo, and meanwhile these stem cells have the capacity of self-remaining. Gene mutations would disturb the above cell differentiation process, leading to the infinite proliferation of specific blood cells, and thereby causing leukemia.

Scientists have confirmed that genetic variation of C/EBPa protein will cause acute myeloid leukemia (AML) in the latest study, and the pathogenesis excited the researchers a lot. "Although only one out of ten AML patients would have this genetic variation in vivo, we've never given it a thought as a cause of leukemia. After a precise reproduction of this gene mutation on the mouse model, now, we can confirm it does cause leukemia ", says Peppy Kirstetter from EMBL Claus Nerlov Laboratory.

Researchers discovered that, as was different to the general knowledge that it could cause endless proliferation of malignant hematopoietic stem cells, the mutation of C/EBPa only affected the partly differentiated cells thought promoting the recombination and thus self-renewal of these cells. This would produce numerous dysfunctional daughter cells to replace the healthy blood cells, and finally result in the systemic oxygen transport asthenia. “This is the first case of non-stem cell myeloid leukemia in healthy blood system, and it bears far-reaching effect on the development and treatment of leukemia.” says Nerlov.

Usually, scientists think that genetic variation plays a key role in causing leukemia and that it should be the target of medicament. However, Nerlov and his colleagues identified a genetic program that is activated in self-renewing leukemic cells, and it also exists in other similar gene-mutation-caused leukemia. This indicates the types of genetic variation have nothing to do with self renewal and infinite proliferation of leukemic cells, and the more efficient drugs developed in the future should target at molecular pathways shared by different cancer stem cells.