Vikas Bhuria

Immunoglobulin heavy-chain status and stromal interactions shape ferroptosis sensitivity in chronic lymphocytic leukemia

Martin Böttcher, Lea Reemts, Paul J. Hengeveld, Romy Böttcher-Loschinski et autres

Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of clonal B cells. Although targeted therapies have improved outcomes, resistance remains a challenge, particularly in high-risk patients with TP53 mutations or unmutated immunoglobulin heavy-chain variable region (IGHV) genes (U-CLL). Ferroptosis, a regulated, …

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Immunoglobulin heavy-chain status and stromal interactions shape ferroptosis sensitivity in chronic lymphocytic leukemia

Martin Böttcher, Lea Reemts, Paul J. Hengeveld, Romy Böttcher-Loschinski et autres

Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of clonal B cells. Although targeted therapies have improved outcomes, resistance remains a challenge, particularly in high-risk patients with TP53 mutations or unmutated immunoglobulin heavy-chain variable region (IGHV) genes (U-CLL). Ferroptosis, a regulated, …

Integrin-dependence of extramedullary erythropoiesis in the spleen of Jak2-V617F positive myeloproliferative neoplasm in mice

Conny K. Baldauf, Linda Poschmann, Bärbel Edelmann-Stephan, Frank Angenstein et autres

The molecular mechanisms driving splenomegaly in myeloproliferative neoplasms (MPNs) remain poorly understood. Utilizing the Jak2-V617F knock-in mouse model, we investigated the role of β1- and β2-integrins in regulating spleen volume and spleen weight. The response to neutralizing antibodies against VLA-4 and the …

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Activation of integrin signaling up-regulates pro-inflammatory cytokines in JAK2-V617F positive hematopoietic cells

Conny K. Baldauf, Corinna Fahldieck, Alexa Angenstein, Sönke Weinert et autres

BACKGROUND: The JAK2-V617F mutation is the most frequent driver mutation in a group of malignant hematopoietic disorders called myeloproliferative neoplasms (MPN). JAK2-V617F is a somatic mutation originating in a hematopoietic stem cell and results in constitutively activated JAK-STAT signaling. High levels of …

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Harnessing myeloid cells in cancer

Suyeon Park, Ekaterina Pylaeva, Vikas Bhuria, Adriana Rosa Gambardella et autres

Cancer-associated myeloid cells due to their plasticity play dual roles in both promoting and inhibiting tumor progression. Myeloid cells with immunosuppressive properties play a critical role in anti-cancer immune regulation. Cells of different origin, such as tumor associated macrophages (TAMs), tumor associated …

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A Study on Experimentally Induced Thrombus Formation in JAK2-V617F and Calr-del52 Mouse Models Using Ligation of the Inferior Vena Cava (IVC)

Vikas Bhuria, Martin Böttcher, Vanja Zeremski, Andreas J. Müller et autres

Introduction Arterial and venous thrombosis represent significant causes of mortality and morbidity in patients with Myeloproliferative Neoplasms (MPNs). While aberrant platelet and leukocyte activity has been identified as important cellular switchboards, the precise molecular chronology of pathologic blood coagulation in MPNs remains …

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Neutrophil-specific expression of JAK2-V617F or CALRmut induces distinct inflammatory profiles in myeloproliferative neoplasia

Tobias Ronny Haage, Emmanouil Charakopoulos, Vikas Bhuria, Conny K. Baldauf et autres

BACKGROUND: Neutrophils play a crucial role in inflammation and in the increased thrombotic risk in myeloproliferative neoplasms (MPNs). We have investigated how neutrophil-specific expression of JAK2-V617F or CALRdel re-programs the functions of neutrophils. METHODS: Ly6G-Cre JAK2-V617F and Ly6G-Cre CALRdel mice were generated. …

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Activating mutations in JAK2 and CALR differentially affect intracellular calcium flux in store operated calcium entry

Vikas Bhuria, Tobias J. Franz, Conny K. Baldauf, Martin Böttcher et autres

Abstract Background Calcium (Ca2+) signaling regulates various vital cellular functions, including integrin activation and cell migration. Store-operated calcium entry (SOCE) via calcium release-activated calcium (CRAC) channels represents a major pathway for Ca2+ influx from the extracellular space in multiple cell types. The …

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Novel Adiponectin Receptor Agonist Inhibits Cholangiocarcinoma via Adenosine Monophosphate-activated Protein Kinase

Khắc Cường Bùi, Mai Ly Thi Nguyen, Samarpita Barat, Tim Scholta et autres

Background: Cholangiocarcinoma (CCA) has a poor prognosis and only limited palliative treatment options. The deficiency of adiponectin and adenosine monophosphate-activated protein kinase (AMPK) signaling was reported in several malignancies, but the alteration of these proteins in CCA is still unclear. Objectives:: This …

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Proteomic Profiling and Cytokine Analysis Reveals Molecular Signatures and Inflammatory Factors Associated with Thrombosis in JAK2-V617F Positive Myeloproliferative Neoplasm (MPN) Cohorts

Vikas Bhuria, Marco van Ham, Katrin Vogel, Ana M. Waldleben et autres

Background: Myeloproliferative neoplasms (MPNs), a hematological malignancy commonly associated with the JAK2-V617F mutation, exhibit a considerable burden of comorbidities resulting from inflammation-mediated processes. The JAK2-V617F malignant clones instigate systemic inflammation by upregulating various pro-inflammatory cytokines. This leads to dysregulated immune and inflammatory …

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P1004: ACTIVATING MUTATIONS IN JAK2 AND CALR DIFFERENTIALLY AFFECT INTRACELLULAR CALCIUM LEVELS AND CALCIUM FLUX

Vikas Bhuria, Tobias J. Franz, Conny K. Baldauf, Martin Böttcher et autres

Topic: 15. Myeloproliferative neoplasms - Biology & Translational Research Background: In myeloproliferative neoplasms (MPNs), mutations in Janus kinase 2 (JAK2), calreticulin (CALR), and the thrombopoietin receptor (MPL) activate common Janus kinase/signal transducer and activator of transcription signaling (JAK/STAT) pathways. These mutations confer …

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Genetic Knock-out of TNFR1 and TNFR2 in a JAK2-V617F Polycythemia Vera Mouse Model

Peter Müller, Conny K. Baldauf, Tobias Ronny Haage, Emmanouil Charakopoulos et autres

Myeloproliferative neoplasms (MPN) are a group of hematological disorders characterized by myeloid cell expansion including erythrocytes, thrombocytes, and leukocytes.1 Besides mutations in JAK2, MPL, or calreticulin, chronic inflammation, including high serum levels of proinflammatory cytokines, plays a pivotal role in the pathophysiology …

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