University of Queensland
Inhibiting the interaction of 2 proteins can prevent the development of acute myeloid leukemia (AML), according to a study published in Blood.
Researchers found evidence to suggest the “docking” of one protein, Myb, with another, p300, is essential for AML development.
“Our data identifies the critical role of this Myb-p300 interaction and shows that the disruption of this interaction could lead to a potential therapeutic strategy,” said Tom Gonda, PhD, of the University of Queensland’s School of Pharmacy in Woolloongabba, Queensland, Australia.
“This finding could lead to our team developing a drug to block this interaction and stop the growth of not only acute myeloid leukemia cells but probably the cells of other types of leukemia as well.”
Dr Gonda and his colleagues conducted this research using cells from Booreana mice, which carry a mutant allele of Myb, as well as cells from wild-type mice.
Experiments showed that the Myb-p300 interaction was necessary for in vitro transformation by the oncogenes AML1-ETO, AML1-ETO9a, MLL-ENL, and MLL-AF9.
The researchers also transduced cells from Booreana mice and wild-type mice with either AML1-ETO9a or MLL-AF9 retroviruses and transplanted the cells into irradiated mice. The cells from wild-type mice generated leukemia in the recipients, but the Booreana cells did not.
Lastly, the team performed gene expression analyses to gain more insight into the Myb-p300 relationship. They found that several genes already implicated in myeloid leukemogenesis and hematopoietic stem cell function are regulated in an Myb-p300-dependent manner.
The researchers therefore concluded that the Myb-p300 interaction is important to myeloid leukemogenesis. And disrupting this interaction could prove useful in the fight against AML.
Dr Gonda pointed out, however, that the Myb protein is produced by the MYB oncogene. And although this oncogene is required for the continued growth of leukemia cells, it is also essential for normal blood cell formation.
“[S]o we need an approach for targeting it that won’t completely disrupt normal blood cell production,” he said. “Our research shows that normal blood cells can continue to form even when the Myb-p300 interaction is unable to occur, suggesting that a drug that blocks the interaction could be safe for use in patients.”
Dr Gonda and his colleagues are also planning to examine the possibility of targeting genes and proteins that work downstream of MYB.
