Alexander Vdovin

University Hospital Ostrava · Blood Cancer Research Group (BCRG)

Induction therapy followed by CD34 ⁺ cell mobilisation and autologous transplantation represents standard of care for multiple myeloma (MM). However, the anti‐CD38 monoclonal antibodies daratumumab and isatuximab have been associated with mobilisation impairment, yet the mechanism remains unclear. In this study, we investigated the effect of three...

Gene expression is a fundamental process that enables cells to produce specific proteins in a timely and spatially dependent manner. In eukaryotic cells, the complex organization of the cell body requires precise control of protein synthesis and localization. Certain mRNAs encode proteins with an N-terminal signal sequences that direct the translat...

Gene expression resulting in the generation of new proteins is a fundamental process critical for every living organism. Particularly in eukaryotic cells, complex organization of the cell body requires fine-tuning of every step prior to de novo protein synthesis. To ensure proper localization, certain mRNAs possess unique signal sequence, which des...

During innate immune responses, myeloid differentiation primary response 88 (MyD88) functions as a critical signaling adaptor protein integrating stimuli from toll-like receptors (TLR) and the interleukin-1 receptor (IL-1R) family and translates them into specific cellular outcomes. In B cells, somatic mutations in MyD88 trigger oncogenic NF-κB sig...

OTUD1 is a deubiquitinating enzyme involved in many cellular processes including cancer and innate, immune signaling pathways. Here, we perform a proximity labeling-based interactome study that identifies OTUD1 largely present in the translation and RNA metabolism protein complexes. Biochemical analysis validates OTUD1 association with ribosome sub...

Serum monoclonal immunoglobulin (Ig) is the main diagnostic factor for patients with multiple myeloma (MM), however its prognostic potential remains unclear. On a large MM patient cohort (n = 4146), we observe no correlation between serum Ig levels and patient survival, while amount of intracellular Ig has a strong predictive effect. Focused CRISPR...

Introduction Monoclonal immunoglobulin (Ig) is a valuable diagnostic marker in patients with multiple myeloma (MM). An inevitable consequence of extensive Ig synthesis is overload of misfolded proteins that saturate proteasome capacity making the myeloma cells highly sensitive to proteasome inhibitors (PI). Even though PI are regularly used in the...

The reason why a few myeloma cells egress from the bone marrow (BM) into peripheral blood (PB) remains unknown. Here, we investigated molecular hallmarks of circulating tumor cells (CTCs) to identify the events leading to myeloma trafficking into the bloodstream. After using next-generation flow to isolate matched CTCs and BM tumor cells from 32 pa...

Introduction Multiple myeloma (MM) being one of the most widely spread haematological malignancies remains an incurable disease. As malignant plasma cells produce abnormally large amounts of immunoglobulins they particularly rely on the ubiquitin-proteasome system (UPS) to avoid aberrant protein overload. This unique feature is targeted by proteaso...

Background. The number of CTC predicts risk of transformation in smoldering MM and survival in active MM. Growing evidence suggests that as the tumor progresses and the microenvironment becomes hypoxic, clonal plasma cells (PC) constantly invade new regions of the bone marrow (BM) through induced systemic recirculation. Of note, the frequency of CT...