Article
Medicine, Research & Experimental
Lakshmi Reddy Palam, Baskar Ramdas, Katelyn Pickerell, Santhosh Kumar Pasupuleti, Rahul Kanumuri, Annamaria Cesarano, Megan Szymanski, Bryce Selman, Utpal P. Dave, George Sandusky, Fabiana Perna, Sophie Paczesny, Reuben Kapur
Summary: Loss of function mutations in DNMT3A are commonly found in AML patients with normal cytogenetics and are associated with poor prognosis. In this study, we found that loss of Dnmt3a resulted in myeloproliferation and hyperactivation of the PI3K pathway. Treatment with PI3K inhibitors partially corrected myeloproliferation, with the alpha/beta inhibitor being more effective. Additionally, PI3K inhibitor treatment prolonged survival and reduced leukemic burden in a human DNMT3A mutant AML model.
Article
Cell & Tissue Engineering
Roshina Thapa, Erez Elfassy, Leonid Olender, Omri Sharabi, Roi Gazit
Summary: Adult hematopoietic stem cells (HSCs) in the bone marrow (BM) are quiescent, but can be activated by perturbations such as blood loss or infection. The earliest stages of HSC activation are not well understood. Surface markers CD69 and CD317 show a response as early as 2 h after stimulation, with varying expression patterns depending on the type of immune stimuli.
STEM CELL RESEARCH & THERAPY
(2023)
Review
Biochemistry & Molecular Biology
Yammy Yung, Emily Lee, Hiu-Tung Chu, Pui-Kwan Yip, Harinder Gill
Summary: Myeloproliferative neoplasms (MPNs) are hematopoietic stem cell disorders characterized by clonal myeloproliferation. Despite effective treatment, complete eradication of CML/MPN stem cells is rare. Novel agents and combination therapy have potential to target abnormal hematopoietic stem cells and the sustaining bone marrow microenvironment in CML and MPNs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Sasja Blokzijl-Franke, Bas Ponsioen, Stefan Schulte-Merker, Philippe Herbomel, Karima Kissa, Suma Choorapoikayil, Jeroen den Hertog
Summary: The study found that HSPCs in mutant zebrafish embryos lacking pten function exhibited death during development, which could be rescued by inhibiting PI3K, while inhibiting PI3K in wild-type embryos also induced HSPC death. PI3K signaling tightly controls HSPC survival, with both up- and downregulation of the signaling pathway reducing stemness of HSPCs.
Article
Hematology
Yang Liu, Qi Chen, Hyun-Woo Jeong, Dong Han, Joerg Fabian, Hannes C. A. Drexler, Martin Stehling, Hans R. Schoeler, Ralf H. Adams
Summary: This study reveals that dopamine derived from sympathetic nerves directly controls the behavior of hematopoietic stem and progenitor cells through D-2 subfamily dopamine receptors. Dopamine signaling affects proliferation, frequency, and transplantation efficiency of HSPCs.
Article
Multidisciplinary Sciences
Lu Cui, Ignacio Moraga, Tristan Lerbs, Camille Van Neste, Stephan Wilmes, Naotaka Tsutsumi, Aaron Claudius Trotman-Grant, Milica Gakovic, Sarah Andrews, Jason Gotlib, Spyros Darmanis, Martin Enge, Stephen Quake, Ian S. Hitchcock, Jacob Piehler, K. Christopher Garcia, Gerlinde Wernig
Summary: The study developed a series of surrogate protein ligands that can modulate TPO-R signaling, preserving HSC properties and inhibiting oncogenic signaling through TPO-R by tuning downstream responses.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Chiara Pastorio, Sara Torres-Rusillo, Juan Ortega-Vidal, M. Carmen Jimenez-Lopez, Inmaculada Ianez, Sofia Salido, Manuel Santamaria, Joaquin Altarejos, Ignacio J. Molina
Summary: Olive oil contains (-)-oleocanthal (OLC), which has been found to have anti-inflammatory, antioxidant, and antitumor activities. This study examined the effects of OLC on various cell lines and found that it inhibits cell proliferation and induces apoptotic death. Hematopoietic tumor cell lines were the most sensitive to OLC treatment. The mechanisms of OLC-mediated cell death involve caspase-dependent and independent pathways.
Article
Hematology
Brian Estevez, Sara Borst, Danuta Jarocha, Varun Sudunagunta, Michael Gonzalez, James Garifallou, Hakon Hakonarson, Peng Gao, Kai Tan, Paul Liu, Sumedha Bagga, Nicholas Holdreith, Wei Tong, Nancy Speck, Deborah L. French, Paul Gadue, Mortimer Poncz
Summary: Patients with familial platelet disorder with a predisposition to myeloid malignancy (FPDMM) have been found to exhibit defective platelet production, which may be corrected by targeting the JNK and TGF-beta 1 pathways.
Article
Multidisciplinary Sciences
Aashirwad Shahi, Jacob Kahle, Chandler Hopkins, Maria Diakonova
Summary: This study elucidates the diverse functions of JAK2 in cells, including involvement in cell proliferation, cell cycle regulation, and centrosome amplification. The SH2 domain and kinase activity play crucial roles in the centrosome localization of JAK2 and regulation of cell growth.
Article
Cell & Tissue Engineering
Han-Sol So, Min-Guk Kim, Jeong-Chae Lee, Sung-Ho Kook
Summary: The study found that using glucose oxidase (GO) can effectively promote the mobilization of hematopoietic stem progenitor cells (HSPCs) from the bone marrow to peripheral blood, even in animal models. Through combined use with granulocyte colony-stimulating factor (G-CSF) and/or AMD3100, the mobilization of HSPCs can be greatly enhanced.
STEM CELLS TRANSLATIONAL MEDICINE
(2021)
Article
Oncology
Srdan Verstovsek, Jean-Jacques Kiladjian, Alessandro M. M. Vannucchi, Ruben A. A. Mesa, Peg Squier, J. E. Hamer-Maansson, Claire Harrison
Summary: This study analyzed the impact of the timing of ruxolitinib treatment on clinical outcomes in patients with intermediate-2 and high-risk myelofibrosis. The results showed that patients who initiated treatment earlier had better outcomes in terms of thrombocytopenia and anemia, higher spleen volume response, and longer overall survival.
Article
Immunology
Haoyue Liang, Weichao Fu, Wenying Yu, Zhijie Cao, Ertao Liu, Fanfan Sun, Xiaodong Kong, Yingdai Gao, Yuan Zhou
Summary: This study compares the mitochondrial functions of different subsets of lymphocytes at different stages of differentiation and activation. B cells were found to have relatively high mitochondrial metabolic activity, while mature B cells showed lower levels. Naive CD4(+) T cells also exhibited relatively high mitochondrial metabolism. Memory CD8(+) T cells had high mitochondrial mass and membrane potential but low mitophagy levels. The study also analyzed the involvement of autophagy-related genes in different lymphocyte subsets, highlighting the heterogeneity of mitophagy pathways.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Carsten Riether
Summary: Adult bone marrow hematopoietic stem cells (HSCs) maintain their function through interactions with regulatory T cells (Tregs). In leukemia, these regulatory mechanisms are disrupted, leading to compromised treatment outcomes.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Talita A. M. Vrechi, Anderson H. F. F. Leao, Ingrid B. M. Morais, Vanessa C. Abilio, Antonio W. Zuardi, Jaime Eduardo C. Hallak, Jose Alexandre Crippa, Claudia Bincoletto, Rodrigo P. Ureshino, Soraya S. Smaili, Gustavo J. S. Pereira
Summary: CBD activates autophagy through ERK1/2 activation and AKT suppression, dependent on ULK1 but independent of mTORC1, suggesting a potential non-canonical pathway and highlighting CBD as a potential therapeutic target for neurodegenerative disorders.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
So-Yeon Park, Jee-Heun Kim, Jang-Hyun Choi, Choong-Jae Lee, Won-Jae Lee, Sehoon Park, Zee-Yong Park, Jeong-Heum Baek, Jeong-Seok Nam
Summary: This study highlights the important role of lipid rafts (LRs) in colorectal cancer, where an LR-disrupting alkylphospholipid drug can suppress CSC populations and their self-renewal activities. By inhibiting the LR/CHEK1 axis, the drug forces CSCs to enter inappropriate mitosis, leading to catastrophic cell death.
CLINICAL AND TRANSLATIONAL MEDICINE
(2021)