FROM ROUTINE DIAGNOSTICS TO DISEASE BIOLOGY
We use and investigate parameters obtained during a routine clinical patient work up to generate hypotheses and elucidate the biology of myeloid neoplasms.
We have shown that JAK2 mutated myeloproliferative neoplasms (MPNs) can transform to JAK2 unmutated acute myeloid leukemia (Theocharides et al., Blood 2007). Today, we know that this phenomenon reflects clonal heterogeneity at the hematopoietic stem cell level. More recently, we elucidated the mechanism of myeloperoxidase deficiency in patients with MPNs (Theocharides et al., Blood 2016). By investigating a large cohort of MPN patients with a routine cell counter method we showed that homozygous mutations in the endoplasmic resident chaperone calreticulin lead to this phenomenon. Finally, we describe for the first time that germline mutations in GATA2 can predispose to MPNs (Rütsche et al., Blood advances 2021, in press).
These investigations show that diagnostic and clinical observations can hint towards mechanisms that lead to disease. At the department of medical oncology and hematology we have access to large cohort and biobank of patients with hemato-oncological malignancies. Together with our diagnostics department this represents a unique opportunity to perform translational research in myeloid diseases.