Focus Research

The Molecular Hematology Group, founded in 2023, primarily focuses on molecular genetic research in hematologic neoplasms and hereditary hematologic disorders. As part of the BLOOD Cluster of the Department of Hematology (UKH-HZL) and through collaboration with various partners, our research is oriented towards practical applications and developments for routine diagnostics and research.

We employ variety of molecular genetic analysis methods, including quantitative PCR, digital PCR and next generation sequencing (NGS) are used. Our group contributes to the BLOOD Research Program of the Department of BioMedical Research (DBMR) at the University of Bern, supporting the faculty of medicine's study programs and offering opportunities for Master's, MD, or PhD theses in our group.

In addition to conducting research in our own projects, we provide project-specific analytics and results evaluations as a partner for genomic diagnostics in hematology, supporting research projects, development, training, and education. We focus on the development, implementation, and validation of new genomic analyses tailored to the needs of the clinic, other research groups or clinical trials. Furthermore, we support interdisciplinary diagnostic-therapeutic boards and the routine laboratory of hematologic genomic analytics at the CGL in the validation, interpretation, and reporting of results from molecular analyses.

Brief descriptions of the 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 erythrozytosis.

Jalowiec et al., 2022

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 the 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.

 

Pabst et al., 2020

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.

Rebmann et al., 2022

CHIP and thrombosis in MPN

CHIP 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.

Publications

Naomi Porret - Search Results - PubMed (nih.gov)
Gertrud Wiedemann - Search Results - PubMed (nih.gov)

  • Perroud, C., Thurian, D., Andres, M., Künzi, A., Wiedemann, G., Zeerleder, S., Bacher, U., Pabst, T., Banz, Y., Porret, N., & Rebmann, E. (2023). Effect of MAPK activation via mutations in NRAS, KRAS and BRAF on clinical outcome in newly diagnosed multiple myeloma. Hematological oncology, 41(5), 912–921. doi.org/10.1002/hon.3208
  • Dorenkamp, M., Porret, N., Diepold, M., & Rovó, A. (2023). A De Novo Frameshift Mutation in RPL5 with Classical Phenotype Abnormalities and Worsening Anemia Diagnosed in a Young Adult-A Case Report and Review of the Literature. Medicina (Kaunas, Lithuania), 59(11), 1953. doi.org/10.3390/medicina59111953
  • Messerli, C., Wiedemann, G., Porret, N., Nagler, M., Seipel, K., Jeker, B., Novak, U., Zeerleder, S., Bacher, U., & Pabst, T. (2023). Correlation of Peripheral Chimeric Antigen Receptor T-cell (CAR-T Cell) mRNA Expression Levels with Toxicities and Outcomes in Patients with Diffuse Large B-cell Lymphoma. Turkish journal of haematology : official journal of Turkish Society of Haematology, 40(3), 187–196. doi.org/10.4274/tjh.galenos.2023.2023.0136
  • Hu, R., Li, X., Hu, Y., Zhang, R., Lv, Q., Zhang, M., Sheng, X., Zhao, F., Chen, Z., Ding, Y., Yuan, H., Wu, X., Xing, S., Yan, X., Bao, F., Wan, P., Xiao, L., Wang, X., Xiao, W., Decker, E. L., … Wiedemann, G., … He, Y. (2023). Adaptive evolution of the enigmatic Takakia now facing climate change in Tibet. Cell, 186(17), 3558–3576.e17. doi.org/10.1016/j.cell.2023.07.003
  • Sanoyan, D. A., Seipel, K., Bacher, U., Kronig, M. N., Porret, N., Wiedemann, G., Daskalakis, M., & Pabst, T. (2023). Real-life experiences with CAR T-cell therapy with idecabtagene vicleucel (ide-cel) for triple-class exposed relapsed/refractory multiple myeloma patients. BMC cancer, 23(1), 345. doi.org/10.1186/s12885-023-10824-3
  • Wittibschlager, V., Bacher, U., Seipel, K., Porret, N., Wiedemann, G., Haslebacher, C., Hoffmann, M., Daskalakis, M., Akhoundova, D., & Pabst, T. (2023). CAR T-Cell Persistence Correlates with Improved Outcome in Patients with B-Cell Lymphoma. International journal of molecular sciences, 24(6), 5688. doi.org/10.3390/ijms24065688
  • Andina, N., de Meuron, L., Schnegg-Kaufmann, A. S., Sarangdhar, M. A., Ansermet, C., Bombaci, G., Batta, K., Keller, N., Porret, N. A., Angelillo-Scherrer, A., Bonadies, N., & Allam, R. (2023). Increased Inflammasome Activation Is Associated with Aging and Chronic Myelomonocytic Leukemia Disease Severity. Journal of immunology (Baltimore, Md. 1950), 210(5), 580–589. doi.org/10.4049/jimmunol.2200412
  • Perroud, C., Porret, N., & Rovó, A. (2023). "The Long Journey of Unexplained Erythrocytosis": Erythrocytosis due to High-Oxygen Affinity Hemoglobinopathy - Hemoglobin Variant Little Rock (HBB: c.432C>A) - A Report of a Swiss Family and Review of the Literature. Acta haematologica, 146(4), 326–330. doi.org/10.1159/000530240
  • Rebmann Chigrinova, E., Porret, N. A., Andres, M., Wiedemann, G., Banz, Y., Legros, M., Pollak, M., Oppliger Leibundgut, E., Pabst, T., & Bacher, U. (2022). Correlation of plasma cell assessment by phenotypic methods and molecular profiles by NGS in patients with plasma cell dyscrasias. BMC medical genomics, 15(1), 203. doi.org/10.1186/s12920-022-01346-1
  • Heini, A. D., Bacher, U., Porret, N., Wiedemann, G., Legros, M., Stalder Zeerleder, D., Seipel, K., Novak, U., Daskalakis, M., & Pabst, T. (2022). Experiences with Glofitamab Administration following CAR T Therapy in Patients with Relapsed Mantle Cell Lymphoma. Cells, 11(17), 2747. doi.org/10.3390/cells11172747
  • Heini, A. D., Bacher, U., Kronig, M. N., Wiedemann, G., Novak, U., Zeerleder, S., Mansouri Taleghani, B., Daskalakis, M., & Pabst, T. (2022). Chimeric antigen receptor T-cell therapy for relapsed mantle cell lymphoma: real-world experience from a single tertiary care center. Bone marrow transplantation, 57(6), 1010–1012. doi.org/10.1038/s41409-022-01658-x
  • Vrotniakaite-Bajerciene, K., Tritschler, T., Jalowiec, K. A., Broughton, H., Brodard, J., Porret, N. A., Haynes, A., Rovo, A., Kremer Hovinga, J. A., Aujesky, D., & Angelillo-Scherrer, A. (2022). Thrombophilia Impact on Treatment Decisions, Subsequent Venous or Arterial Thrombosis and Pregnancy-Related Morbidity: A Retrospective Single-Center Cohort Study. Journal of clinical medicine, 11(14), 4188.
  • Jalowiec, K. A., Vrotniakaite-Bajerciene, K., Jalowiec, J., Frey, N., Capraru, A., Wojtovicova, T., Joncourt, R., Angelillo-Scherrer, A., Tichelli, A., Porret, N. A., & Rovó, A. (2022). JAK2 Unmutated Polycythaemia-Real-World Data of 10 Years from a Tertiary Reference Hospital. Journal of clinical medicine, 11(12), 3393. doi.org/10.3390/jcm11123393
  • Rentsch, V., Seipel, K., Banz, Y., Wiedemann, G., Porret, N., Bacher, U., & Pabst, T. (2022). Glofitamab Treatment in Relapsed or Refractory DLBCL after CAR T-Cell Therapy. Cancers, 14(10), 2516. doi.org/10.3390/cancers14102516
  • Seipel, K., Porret, N., Wiedemann, G., Jeker, B., Bacher, V. U., & Pabst, T. (2022). sBCMA Plasma Level Dynamics and Anti-BCMA CAR-T-Cell Treatment in Relapsed Multiple Myeloma. Current issues in molecular biology, 44(4), 1463–1471. doi.org/10.3390/cimb44040098
  • Shumilov, E., Mazzeo, P., Zinkernagel, M. S., Legros, M., Porret, N., Romagna, L., Haase, D., Lenz, G., Novak, U., Banz, Y., Pabst, T., & Bacher, U. (2022). Comprehensive Laboratory Diagnostic Workup for Patients with Suspected Intraocular Lymphoma including Flow Cytometry, Molecular Genetics and Cytopathology. Current oncology (Toronto, Ont.), 29(2), 766–776. doi.org/10.3390/curroncol29020065
  • Lötscher, F., Seitz, L., Simeunovic, H., Sarbu, A. C., Porret, N. A., Feldmeyer, L., Borradori, L., Bonadies, N., & Maurer, B. (2022). Case Report: Genetic Double Strike: VEXAS and TET2-Positive Myelodysplastic Syndrome in a Patient With Long-Standing Refractory Autoinflammatory Disease. Frontiers in immunology, 12, 800149. doi.org/10.3389/fimmu.2021.800149
  • Rempfer, C., Wiedemann, G., Schween, G., Kerres, K. L., Lucht, J. M., Horres, R., Decker, E. L., & Reski, R. (2022). Autopolyploidization affects transcript patterns and gene targeting frequencies in Physcomitrella. Plant cell reports, 41(1), 153–173. doi.org/10.1007/s00299-021-02794-2
  • Jalowiec, K. A., Vrotniakaite-Bajerciene, K., Capraru, A., Wojtovicova, T., Joncourt, R., Rovó, A., & Porret, N. A. (2021). NGS Evaluation of a Bernese Cohort of Unexplained Erythrocytosis Patients. Genes, 12(12), 1951. doi.org/10.3390/genes12121951
  • Müller, J., Porret, N. A., & Rüfer, A. (2021). Identification of a JAK2 FERM Domain Variant Associated With Hereditary Thrombocytosis. HemaSphere, 5(8), e626. doi.org/10.1097/HS9.0000000000000626
  • Chanias, I., Stojkov, K., Stehle, G. T., Daskalakis, M., Simeunovic, H., Njue, L. M., Schnegg-Kaufmann, A. S., Porret, N. A., Allam, R., Rao, T. N., Benz, R., Ruefer, A., Schmidt, A., Adler, M., Rovo, A., Balabanov, S., Stuessi, G., Bacher, U., Bonadies, N., & On Behalf Of The Swiss Mds Study Group (2021). Myelodysplastic Syndromes in the Postgenomic Era and Future Perspectives for Precision Medicine. Cancers, 13(13), 3296. doi.org/10.3390/cancers13133296
  • Heini, A. D., Porret, N., Zenhaeusern, R., Winkler, A., Bacher, U., & Pabst, T. (2021). Clonal Hematopoiesis after Autologous Stem Cell Transplantation Does Not Confer Adverse Prognosis in Patients with AML. Cancers, 13(13), 3190. doi.org/10.3390/cancers13133190
  • Bonadies, N., Rovó, A., Porret, N., & Bacher, U. (2021). When Should We Think of Myelodysplasia or Bone Marrow Failure in a Thrombocytopenic Patient? A Practical Approach to Diagnosis. Journal of clinical medicine, 10(5), 1026. doi.org/10.3390/jcm10051026