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Blood Podcast: Season 1, Episode 48
In this week’s episode, we will review a study that reveals a previously unknown role for the canonical Wnt signaling pathway in the regulation of granulocyte production in steady state and emergency granulopoiesis, examine the discordance in different assays that measure factor VIII activity after adenoviral-associated gene therapy, and learn about the dynamics of declining antibody levels in repeat Covid-19 convalescent plasma donors.
Activity of transgene-produced B-domain–deleted factor VIII in human plasma following AAV5 gene therapy
Rosen and colleagues compared factor VIII level determination by one-step assay versus chromogenic assay and demonstrated that the 2 assays are discrepant, especially when measuring transgenic factor VIII following gene therapy. While both recombinant subcutaneous factor VIII and recombinant factor VIII yield similar results by chromogenic assay, the 1-step assay tends to show higher activity when measuring transgenic factor VIII.
Activation of the receptor tyrosine kinase RET improves long-term hematopoietic stem cell outgrowth and potency
Neuronal signals have been implicated in hematopoietic stem cell (HSC) proliferation. Grey and colleagues demonstrated that HSCs are enriched for expression of RET, a receptor tyrosine kinase activated by glial-derived neurotrophic factor, and that activation of RET improves HSC expansion and transplant potential. This pathway holds promise for promoting ex vivo HSC expansion for stem cell transplantation.
Prediction and prevention of central nervous system relapse in patients with extranodal natural killer/T-cell lymphoma
Extranodal natural killer (NK) T-cell lymphoma is a rare Epstein-Barr virus–positive non-Hodgkin lymphoma. Central nervous system (CNS) relapse is rare but has a terrible prognosis, leading to efforts to identify predictive factors for CNS recurrence. The authors demonstrate that CNS relapse can be predicted by a modification of the prognostic index of natural killer lymphoma score based on the number of extranodal sites. Prophylaxis with intermediate-dose methotrexate may decrease CNS relapse.
β-Catenin–TCF/LEF signaling promotes steady-state and emergency granulopoiesis via G-CSF receptor upregulation
Danek et al demonstrated a role for the canonical Wnt signaling pathway in regulating steady-state and emergency granulopoiesis. The signaling pathway is mediated by interaction between β-catenin and the TCF/LEF transcription factors; mice with a dominant negative form of TCF4 that abrogates this interaction are neutropenic and have reduced neutrophil maturation. The authors confirmed that this is mediated through downregulation of neutrophil-specific gene expression, notably the G-CSF receptor.
What is the future of immunotherapy in multiple myeloma?
In this Blood Spotlight, Rasche and colleagues present the state of the art of immunotherapy for multiple myeloma. They discuss the role of monoclonal antibodies that are part of the new backbone of myeloma therapy and the promise of future T-cell therapies, looking toward a future for a potential cure of the disease with chemotherapy-free regimens.
