Torsten Steinbrunn
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View article: Integrative genomic, single-cell, and functional profiling uncovers immune consequences of the CD48–CD244 axis in NK cells in multiple myeloma
Integrative genomic, single-cell, and functional profiling uncovers immune consequences of the CD48–CD244 axis in NK cells in multiple myeloma Open
Background: Natural killer (NK) cells play a key role in immune surveillance of multiple myeloma (MM), but their function becomes progressively impaired as the disease advances. CD48, one of the most abundant NK-cell ligands on MM cells, e…
Functional genomics studies identify determinants of response vs. resistance to pharmacological inhibitors of KRAS in multiple myeloma Open
Up to 50% of multiple myeloma (MM) patients harbor mutations of KRAS or NRAS. Pharmacologic inhibitors targeting specific KRAS mutations have clinical activity in solid tumors. We evaluated Ras inhibitors in preclinical models of MM, with …
Modeling of a hyper-inflammatory hematopoietic niche ex vivo reveals a multi-step process driving CAR T- cell associated myeloid leukemia in multiple myeloma Open
Introduction: Although prior exposure to mutagenic agents like melphalan and lenalidomide is a known risk factor for post-cytotoxic therapy myeloid neoplasms (MN-pCT) in multiple myeloma (MM), the increased rate of MN-pCTs reported in clin…
Regulatory network analysis identifies changes in ahr, TFAP4, and AP-1 transcription factors as top drivers of symptomatic disease progression in Waldenstrom's macroglobulinemia. Open
Background: We previously described three subtypes of Waldenstrom's Macroglobulinemia (WM) using a multi-omic data set derived from 249 untreated patients with WM who had detectable MYD88 mutations. The B-cell like (BCL) and Plasma cell li…
Increased teclistamab dosing interval improves T-cell diversity and reduces infection risk, while T-cell exhaustion remains minimal irrespective of schedule Open
Introduction: Bispecific antibodies are among the most effective treatments for relapsed/refractory multiple myeloma (RRMM), inducing rapid and durable remissions. Yet, most agents, including teclistamab, were developed with short dosing i…
View article: Negative regulators of survival and proliferation (NRSPs) identified by CRISPR activation studies in multiple myeloma (MM) vs. other neoplasias: Therapeutic implications
Negative regulators of survival and proliferation (NRSPs) identified by CRISPR activation studies in multiple myeloma (MM) vs. other neoplasias: Therapeutic implications Open
Background - Methods: Hundreds of cell lines have been examined by genome-sale CRISPR knockout (KO) studies to identify functional drivers of tumors, but only few lines have been systematically examined with CRISPR activation (CRISPRa). We…
Functional Genomics Studies Decipher the Genetic Perturbations and Unravel Mechanisms of Response/Resistance upon Mutant-Specific KRAS Inhibition in Multiple Myeloma Open
INTRODUCTION Mutated RAS, a key oncogenic driver in multiple myeloma (MM), can be present in up to 50% of primary MM. Several novel pharmacological inhibitors developed to target specific KRAS point mutations, have been successfully incorp…
View article: Real-world experience with letermovir for cytomegalovirus-prophylaxis after allogeneic hematopoietic cell transplantation: A multi-centre observational study
Real-world experience with letermovir for cytomegalovirus-prophylaxis after allogeneic hematopoietic cell transplantation: A multi-centre observational study Open
Our study highlights the preventive effects of letermovir on csCMVi after aHCT. A substantial proportion of patients developed a csCMVi after discontinuation of letermovir. In particular, patients with severe neutropenia require specific a…
Clonal competition assays identify fitness signatures in cancer progression and resistance in multiple myeloma Open
Multiple myeloma (MM) is a genetically heterogeneous disease and the management of relapses is one of the biggest clinical challenges. TP53 alterations are established high‐risk markers and are included in the current disease staging crite…
Functional Investigation of IGF1R Mutations in Multiple Myeloma Open
High expression of the receptor tyrosine kinase (RTK) insulin-like growth factor-1 receptor (IGF1R) and RTK mutations are associated with high-risk/worse prognosis in multiple myeloma (MM). Combining the pIGF1R/pINSR inhibitor linsitinib w…
View article: Platelet Subpopulations and Distinct Platelet Function Defects after Hematopoietic Stem Cell Transplantation in Mice and Humans
Platelet Subpopulations and Distinct Platelet Function Defects after Hematopoietic Stem Cell Transplantation in Mice and Humans Open
Allogeneic hematopoietic stem cell transplantation (HSCT) is often accompanied by bleeding complications due to delayed platelet engraftment. Despite having prolonged thrombocytopenia, patients can also develop thrombotic events. The mecha…
Targeting Mutant KRAS with Novel Mutant-Specific Pharmacological Inhibitors: Activity Against Myeloma and Other Lymphoid Malignant Cells and Molecular Mechanisms of Resistance Open
Oncogenic RAS mutations are frequent genomic drivers in hematologic neoplasias such as multiple myeloma (MM) but are traditionally considered non-“druggable”. Novel specific inhibitors of G12C and G12D KRAS mutants are clinically active in…
<i>Functional Characterization of Genes Residing in Chromosomal Regions with “High-Risk” Lesions in Multiple Myeloma</i> Open
The molecular landscape of DNA copy number variants (CNV) in multiple myeloma (MM) has been extensively studied, especially for lesions associated with adverse clinical outcome, e.g., 17p13(del) and 1p32(del) and 1q21(gain/amp). However, f…
View article: Supplement from A GRP78-Directed Monoclonal Antibody Recaptures Response in Refractory Multiple Myeloma with Extramedullary Involvement
Supplement from A GRP78-Directed Monoclonal Antibody Recaptures Response in Refractory Multiple Myeloma with Extramedullary Involvement Open
Supplementary Table 1 Figure S1A, S1B
Supplement from A GRP78-Directed Monoclonal Antibody Recaptures Response in Refractory Multiple Myeloma with Extramedullary Involvement Open
Supplementary Table 1 Figure S1A, S1B
Data from A GRP78-Directed Monoclonal Antibody Recaptures Response in Refractory Multiple Myeloma with Extramedullary Involvement Open
Purpose: Glucose-regulated protein (GRP) 78 is overexpressed in multiple myeloma, and both its surface expression and its biologic significance as key sensor of the unfolded protein response make GRP78 an ideal candidate for immunotherapeu…
Data from A GRP78-Directed Monoclonal Antibody Recaptures Response in Refractory Multiple Myeloma with Extramedullary Involvement Open
Purpose: Glucose-regulated protein (GRP) 78 is overexpressed in multiple myeloma, and both its surface expression and its biologic significance as key sensor of the unfolded protein response make GRP78 an ideal candidate for immunotherapeu…
The Route of the Malignant Plasma Cell in Its Survival Niche: Exploring “Multiple Myelomas” Open
Growing evidence points to multiple myeloma (MM) and its stromal microenvironment using several mechanisms to subvert effective immune and anti-tumor responses. Recent advances have uncovered the tumor-stromal cell influence in regulating …
<sup>68</sup>Ga-Pentixafor PET/CT for Detection of Chemokine Receptor CXCR4 Expression in Myeloproliferative Neoplasms Open
C-X-C motif chemokine receptor 4 (CXCR4) is an attractive target for cancer diagnosis and treatment, as it is overexpressed in many solid and hematologic malignancies. This study investigated the feasibility of CXCR4-directed imaging with …
View article: Halting the vicious cycle within the multiple myeloma ecosystem: blocking JAM-A on bone marrow endothelial cells restores angiogenic homeostasis and suppresses tumor progression
Halting the vicious cycle within the multiple myeloma ecosystem: blocking JAM-A on bone marrow endothelial cells restores angiogenic homeostasis and suppresses tumor progression Open
Interactions of malignant multiple myeloma (MM) plasma cells (MM-cells) with the microenvironment control MM-cell growth, survival, drug-resistance and dissemination. As in MM microvascular density increases in the bone marrow (BM), we inv…
Exon-4 Mutations in KRAS Affect MEK/ERK and PI3K/AKT Signaling in Human Multiple Myeloma Cell Lines Open
Approximately 20% of multiple myeloma (MM) cases harbor a point mutation in KRAS. However, there is still no final consent on whether KRAS-mutations are associated with disease outcome. Specifically, no data exist on whether KRAS-mutations…
RAL GTPases mediate multiple myeloma cell survival and are activated independently of oncogenic RAS Open
Oncogenic RAS provides crucial survival signaling for up to half of multiple myeloma cases, but has so far remained a clinically undruggable target. RAL is a member of the RAS superfamily of small GTPases and is considered to be a potentia…
IKZF1/3 and CRL4<sup>CRBN</sup> E3 ubiquitin ligase mutations and resistance to immunomodulatory drugs in multiple myeloma Open
The work was supported by the Deutsche Forschungsgemeinschaft (KFO216), the IZKF, the\n\t\t\t\t BTHA and the CDW Stiftung (KMK). UM was supported by a grant of the German Excellence\n\t\t\t\t Initiative to the Graduate School of Life Scien…
PS1357 FITNESS SIGNATURES IN MULTIPLE MYELOMA PROGRESSION AND RESISTANCE Open
Background: The amount of descriptive genetic data in multiple myeloma (MM) is growing exponentially. Clonal dynamics leading to disease progression and resistance development are evident and have been described in a number of exemplary MM…
Rare SNPs in receptor tyrosine kinases are negative outcome predictors in multiple myeloma Open
Multiple myeloma (MM) is a plasma cell disorder that is characterized by a great genetic heterogeneity. Recent next generation sequencing studies revealed an accumulation of tumor-associated mutations in receptor tyrosine kinases (RTKs) wh…
A GRP78-Directed Monoclonal Antibody Recaptures Response in Refractory Multiple Myeloma with Extramedullary Involvement Open
Purpose: Glucose-regulated protein (GRP) 78 is overexpressed in multiple myeloma, and both its surface expression and its biologic significance as key sensor of the unfolded protein response make GRP78 an ideal candidate for immunotherapeu…