Genetic cause of blood disease found

Genetic cause of blood disease found

Illuminate newsletter index page, December 2019
December 2019

Dr Melissa Call
Dr Melissa Call was part of a collaboration that identified
genetic mutations involved in myeloproliferative diseases.

Institute researchers have discovered seven new genetic drivers of myeloproliferative diseases – chronic cancer-like blood disorders that can lead to bone marrow failure, stroke and leukaemia.

Myeloproliferative diseases are caused by excess production of mature blood cells in the bone marrow.

The study also uncovered 90 mutations with the potential to make the diseases worse in existing patients. The findings could help clinicians to accurately diagnose patients, as well as lead to new targeted treatments.

Dr Jessica Bridgford, Dr Melissa Call and Associate Professor Matthew Call from the Institute led the study in collaboration with Institute computational biologist Dr Alan Rubin, Dr Andrew Brooks from the University of Queensland, and haematologists based in Italy. The study was published in the journal Blood.

Fast, accurate approach

Study co-lead Dr Melissa Call said the research team focused on a region of the protein called MPL – known to be a hotspot for mutations that cause uncontrolled blood cell growth.

“Using a new technique called ‘deep mutational scanning’ we tested 600 variants of MPL for their potential to cause disease.

“New methods developed by our collaborator, Institute bioinformatician Dr Alan Rubin, enabled us to analyse raw DNA sequencing data and rank all potentially disease-causing mutations from least to most active in driving myeloproliferative diseases.”

Confidence in diagnosis

Collaborating with haematologists in Italy, the researchers confirmed many of the newly identified mutations were present in the DNA of patients with myeloproliferative diseases.

Understanding the disease-causing mutations in individual patients could, in the future, enable researchers to develop therapies that target those mutations, shutting down their harmful effects.