Julian Grabek is one of HSANZ / LF's PhD recipients for 2021, and is showing his research skills already.   His work is on Identifying subclones in early phase MPN that drive progression and leukaemic transformation 

Project summary 

Myeloproliferative neoplasms (MPN) are clonal haematological disorders of stem cells. These stem cells undergo a mutation that drives an overproduction of blood cells.  MPNs include

• polycythemia vera (too many red blood cells),

• essential thrombocythemia (too many platelets) and

• primary myelofibrosis (bone marrow transformation into fibrotic tissue leading to bone marrow failure).

Throughout the course of the disease the stem cells are driven by specific mutations (JAK2, CALR and MPL) but over time additional genetic mutations are acquired leading to progression of the disease to either secondary myelofibrosis and bone marrow failure or acute myeloid leukaemia. These outcomes have limited treatment options and have a poor prognosis.

High risk stem cells with the potential to develop into leukaemia can be identified early in the disease but are often a “needle in a haystack” when compared to the rest of the MPN stem cells.  By using cutting edge single cell technology Dr Grabek will separate each individual cell of the MPN stem cells. Through a combination of mutational analysis by novel nanopore technology and assessment of downstream gene signalling he will be able to determine the early stages of leukaemia development in these disorders. In future, he hopes to establish which treatments have the potential to arrest these early changes and prevent transformation to leukaemia.

for the article on the LF website, click here