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Twin blood cell growth proteins are not identical

01 August 2016

Researchers at the Institute have shown that a pair of proteins involved in the development of blood cells may have different roles to play, with one apparently much more implicated in certain types of leukaemia.

RUNX1 is known as a ‘master regulator’ of blood cell development, primarily in action as an embryo grows. It also controls the accurate production of the various types of blood cells throughout adult life. A significant number of leukaemia cases involve the mutation of RUNX1, but the fully functioning version of the gene is conversely required in some cases to maintain a leukaemic state.

Through the work of ‘promoters’, P1 and P2, RUNX1 is used to generate two different proteins: RUNX1C and RUNX1B respectively. The team from the Stem Cell Biology group labelled the two promoters, to trace their activities in adults.

Dr Georges Lacaud, who led the research, explained: “We’ve previously shown that in embryonic development, P2 is more active early on. This is followed by a boost in P1 activity in the later stages before birth.”

His group showed that RUNX1C dominated – P1 was found throughout the bone marrow. On the other hand, P2 levels appeared to be restricted to only certain cell types, allowing differentiation between platelet-producing cells and red blood cells.

When the scientists removed activity of RUNX1C, they saw a reduction in the production of platelets – a similar situation, although less severe, to when RUNX1 as a whole was lost. Other cell types were less affected.

However, when they investigated the effect of one particular leukaemia gene – AML1-ETO – they saw that it appeared to promote P2 over P1.

“It seems that the two isoforms of Runx1 have different roles to play in both normal blood cell development and leukaemia,” added Dr Lacaud.