Blood Cell Mysteries: How Zebrafish Are Helping Solve Rare Bone Marrow Disorders

At this week’s Symposium on Bone Marrow Syndromes organised by Maddie Riewoldt’s Vision, Professor Graham Lieschke AM will present a unique perspective – from the zebrafish tank.

A clinical haematologist at Peter MacCallum Cancer Centre and the Royal Melbourne Hospital, and group leader at the Australian Regenerative Medicine Institute (ARMI), Professor Lieschke is internationally known for his work on white blood cell development and immune function. His lab has long been at the forefront of using zebrafish to model the genetic machinery of blood cell production and inflammation. But in a recent turn, he’s been applying these tools to a related challenge: understanding the  genetic causes of inherited bone marrow failure syndromes (IBMFS).

These rare, genetically diverse disorders, such as congenital neutropenia and Diamond Blackfan anaemia, impair the bone marrow’s ability to produce healthy blood cells. For affected patients and families, getting an accurate diagnosis is often slow, uncertain, and emotionally exhausting.

That’s where the IBMDx study comes in. Led by Associate Professor Piers Blombery at Peter MacCallum Cancer Centre, with collaborators across clinical haematology, genomics, and pathology from around Australia, this MRFF-funded initiative is using whole genome and transcriptome sequencing to improve the diagnosis of IBMFS and related conditions. Professor Lieschke and his team contribute by taking potential disease-causing variants from patient sequencing data and functionally testing them in zebrafish.

“We are firstly a white blood cell development lab,” he says. “But these collaborations allow us to apply the tools we’ve developed over many years to new questions about other types of blood cells. Zebrafish are remarkably conserved with humans when it comes to blood development and genetic experiments are fast and flexible. That makes them ideal for testing whether a gene variant is clinically significant and those that are just benign background noise.”

Using CRISPR gene-editing – a precise tool for cutting and modifying DNA – Lieschke’s group can rapidly knock out candidate genes in zebrafish embryos to see whether red blood cells, white cells or thrombocytes (the fish equivalent of platelets) are affected. These functional assays help translate sequencing results into diagnostic confidence and sometimes uncover entirely new mechanisms of disease.

One example being presented at the symposium shows how a gene is needed to produce normal thrombocyte numbers. Another shows how a novel variation in the non-coding region of a gene contributes to Diamond Blackfan anaemia in the patient.

“Every rare case like this is also a window into the fundamental biology of how blood forms,” says Professor Lieschke. “They’re biological experiments, in a sense—and they teach us much more than just the answer to a single clinical question.”

Professor Lieschke is keen to ensure the large collaborative team is acknowledged. “I’m not the leader of this project. Our contribution is a small but powerful part, using zebrafish to clarify the functional role of novel variants in a whole animal model.” He adds: “This project shows how bringing together a multidisciplinary team can enable precise genetic diagnosis. That has real value, not just for guiding treatment, but also for deepening our fundamental understanding of how bone marrow produces blood cells.”

He also acknowledges the enduring role of Maddie Riewoldt’s Vision, which supported work in his lab early in the days of the foundation. Professor Lieschke emphasises his continued connection with the Maddie Rewoldt’s Vision community. “They welcomed us in at the start and have continued to involve us,” he says. As the organisation marks its 10th anniversary, the collaboration reflects the kind of patient-focused, cross-disciplinary science that will be critical for the next decade, bringing clarity, connection, and hope to people living with bone marrow failure.

This symposium brings together experts from across the country and keynote speakers from overseas, Lieschke’s observation is clear: basic science, when combined with clinical insight and community backing, can do more than just decode rare diseases. It can bring to patients and their families more timely, accurate, diagnosis and improved care.

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