Ongoing Projects

Our own research projects cover a variety of different topics with a focus on the development and improvement of modern molecular genetic diagnostics and MRD (measureable/minimal residual disease) measurements in hematooncology.

Hereditary erythrocytosis

In recent years, the significance of various germline variants in patients with congenital hematological diseases, such as erythrocytosis, has been recognized for diagnostic, clinical, and research purposes. Addressing these questions requires proper methodology and selection of suitable genes for genetic analysis. Correct variant interpretation in the context of a given clinical presentation is essential but often challenging. Therefore, at our center, genetic analysis results are discussed by a multidisciplinary team together with the clinical specialists.

For patients suffering from unclear persistent polyglobulia, which is not classified as primary (PV with JAK2 mutation or other clonal marker) or secondary (caused by diseases of various other organs), we developed a germline NGS panel covering 13 genes. We are currently screening a patient cohort using an extended version covering 24 genes including PIEZO1. These findings help differentiate between idiopathic and rarely occurring congenital erythrocytosis.

Bone marrow failures

Bone marrow failures (BMF) are part of a complex group of disorders. In order to support comprehensive diagnosis, we have developed NGS for hereditary BMF, and participate in a Swiss interdisciplinary board for patients. 

CAR-T therapy monitoring

In 2019, the first patient in Switzerland received chimeric antigen receptor T-cell (CAR-T) therapy at the Inselspital Bern. Now, this immunotherapy is available for the treatment of a variety of relapsed/refractory B-cell lymphomas (DLBCL NHL, MCL), juvenile ALL and multiple myeloma (MM). For longitudinal monitoring of CAR-T cell expansion and persistence in vivo, we developed sequence specific droplet digital PCR (ddPCR) assays for all constructs currently used at our center. Besides allowing the quantification of CAR-T copy numbers from a variety of patient samples in a routine diagnostic setting, this method helps to understand how CAR-T expansion and persistence is correlated to treatment success, assessment of toxicities, and, additionally, response to treatment with bispecific antibodies upon relapse after CAR-T therapy. Additionally, we were the first to show that CAR-T mRNA expression measured with the ddPCR method indeed shows a high correlation with DNA copy numbers, thus confirming active transgene expression.

We are now exploring circulating lymphoma DNA as a follow-up marker in CAR-T treated DLBCL patients. With this approach, we aim to develop a biopsy-free alternative for sensitive genotyping of circulating tumor DNA in blood samples, a procedure called liquid biopsy, by combining NGS and molecular barcode technologies. This technology then can be used for monitoring of the patients during and after treatment.

This project is generously funded by the Foundation for Clinical-Experimental Cancer Research.

Somatic genetics of plasma cell disorders

Our recent work has shown that there is a complex genetic progression from early plasma cell precursor alterations towards monoclonal gammopathy of unclear significance (MGUS) to symptomatic MM. As there is a correlation of somatic mutations, degree of bone marrow infiltration and clinical data, in future NGS testing could be a part of routine diagnostics and contribute to therapeutic considerations. Currently we are studying the prognostic relevance of TP53 mutations in patients with multiple myeloma or other plasma cell disorders.

CHIP and thrombosis in MPN

CHIP (clonal hematopoiesis of indeterminate potential) involves somatic mutations in hematopoietic stem/progenitor cells without cytopenia/cytoses. We are establishing a database of patients with MPN driver mutations (JAK2 V617F, CALR, MPL) to identify patients with present or absent MPN features and assess thrombosis incidence and CHIP progression.

We are always open to discuss project ideas with interested partners from the clinic, other research groups or clinical studies.