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CPSF6-RARγ interacts with histone deacetylase 3 to promote myeloid transformation in RARG-fusion acute myeloid leukemia.

Nat Commun

January 2025

National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.

Acute myeloid leukemia (AML) with retinoic acid receptor gamma (RARG) fusions, which exhibits clinical features resembling acute promyelocytic leukemia (APL), has been identified as a new subtype with poor clinical outcomes. The underlying mechanism of RARG-fusion leukemia remains poorly understood, and needs to be explored urgently to instruct developing effective therapeutic strategies. Here, using the most prevalent RARG fusion, CPSF6-RARG (CR), as a representative, we reveal that the CR fusion, enhances the expansion of myeloid progenitors, impairs their maturation and synergizes with RAS mutations to drive more aggressive myeloid malignancies.

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Microthrombus formation is associated with COVID-19 severity; however, the detailed mechanism remains unclear. In this study, we investigated mouse models with severe pneumonia caused by SARS-CoV-2 infection by using our in vivo two-photon imaging system. In the lungs of SARS-CoV-2-infected mice, increased expression of adhesion molecules in intravascular neutrophils prolonged adhesion time to the vessel wall, resulting in platelet aggregation and impaired lung perfusion.

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Platelets are hyperactive in patients with type2 diabetes (T2DM), they adhere to vascular endothelium and play a key role in macrovascular complications. Platelets activity can be measured by flow-cytometry (cluster of differentiation (CD) 41, CD 42, CD 62, CD 63), which allows detection of surface antigens in a sensitive and specific manner. This study aimed to describe platelets activity in T2DM in association with cardiovascular and cerebrovascular complications in relation to duration of diabetes (DM).

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The contemporary concept of carcinogenesis summarizes the role of hypoxia, neoangiogenesis, and hemostasis, including in the stage of progression and metastasis of the tumor process. Metastatic disease is a serious therapeutic challenge for any oncological condition. The purpose of this study was to evaluate the dynamics of specific indicators of neoangiogenesis and hypoxia as potential biomarkers for therapeutic efficacy or risk of disease progression in patients with brain metastases (BM) undergoing robotic stereotactic radiosurgery.

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Splanchnic vein thrombosis (SVT), which is particularly prevalent in myeloproliferative neoplasms (MPNs), has a multifactorial pathomechanism involving the anticoagulant protein C (PC) pathway. To better characterize the hypercoagulable state in SVT we assessed its key enzymes thrombin and activated PC (APC). The study population included 73 patients with SVT, thereof 36 MPN+, confirmed by bone marrow biopsy, 37 MPN-, and 30 healthy controls.

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