The study, done on mice, suggests a stem cell protein called Asrij is a novel regulator of wild type tumor suppressor p53 stability in hematopoietic stem cells (HSCs).
It could help design targeted therapies for myeloproliferative disease, a group of slow-growing blood cancers, according to researchers, including Maneesha S. Inamdar from the Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR) in Bengaluru.
"We provide a new mouse model resembling myeloproliferative disease and identify a post-translational regulator of wild type p53 essential for maintaining HSC quiescence that could be a potential target for pharmacological intervention," the team said.
According to the study, inactivation of the tumor suppressor p53 is essential for unrestrained growth of cancers. But only 11 percent of hematological malignancies has mutant p53.
Mechanisms that cause wild type p53 dysfunction and promote leukemia are inadequately deciphered, suggests the study.
The stem cell protein Asrij is misexpressed in several human hematological malignancies and implicated in the p53 pathway and DNA damage response, the team said.
For the study, the team generated the first Asrij null (knockout, KO) in mice and showed they are viable and fertile with no gross abnormalities. However, by six months, they exhibited increased peripheral blood cell counts, splenomegaly and expansion of bone marrow HSCs with a higher myeloid output.