The team, led by Maneesha S Inamdar at Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), has published its findings in ‘Blood’, a journal of the American Society of Haematology.
Inamdar, whose lab has discovered a stem cell protein called asrij (blood in Sanskrit), has found it plays a key role in preventing myelo-proliferative disease — a condition characterised by excessive production of mature blood cells.
Producing new blood cells is a lifelong activity. Given the sheer number of cells, they are prone to mutation which then becomes cancerous.
90% cancers caused by p53 mutation
Now, 90% of solid cancers are known to be caused by the mutation of p53, a protein that regulates cells production. In case of blood cancer, only 11% of the cancer was seen to be caused by p53 mutation. “Despite no significant mutation of p53, we found levels of asrij were low, causing uncontrolled production of new cells,” Inamdar told TOI.
Saloni Sinha, first author of the paper, said asrij protects p53, a cancer-preventing protein also known as the ‘Guardian of the Genome’. “Without asrij, p53 is destroyed and blood stem cells proliferate and become cancerous. It is known that mutations in p53 lead to cancer. However, scientists have been puzzled about how some cancers develop without a mutation in p53. Our work explains how this can happen,” Saloni said.
Will lead to new diagnostics
Inamdar said this could pave the way to new diagnostics and lead to the cure. To study how asrij works, the team designed a mouse that is engineered to mark the asrij gene for deletion. This was done in collaboration with the RIKEN CDB, Kobe,
Japan and the National Centre for Biological Sciences, Bengaluru.
The Inamdar laboratory then deleted the marked region and showed that deleting one or both copies of the gene has no apparent effect, which was perplexing. Based on their earlier work, they predicted the mice are likely to develop blood cancer.
“Detailed experiments, including bone marrow transplants in mice, showed the mutants had too many blood stem cells, an enlarged spleen and developed severe myeloproliferative disease as they aged, just like human patients. The study could potentially revolutionise research seeking to find the origin and clinical progression of blood and other cancers. It will also lead to a search for drug treatments for a wide range of diseases affected by asrij and p53, including cancers and neuro-degenerative disorders,” said Inamdar.