Article
Medical Laboratory Technology
Jiang Yu, Wen-XU Chen, Wen-Jing Xie, Rong-Wei Chen, Dan-Qi Lin, Wei-Wei You, Wei-Lin Ye, Hong-Qin Zhang, Dong-Hong Lin, Jian-Ping Xu
Summary: Silencing of CrkL effectively increases apoptosis induced by doxorubicin and reverses doxorubicin resistance in K562/ADR cells. Knockdown CrkL suppresses the PI3K/Akt/MRP1 signaling pathway, indicating a potential novel strategy for intervention chemoresistance in myelogenous leukemia during chemotherapy. Overexpression of MRP1 reduces apoptosis rate and reverses inhibitory effects of doxorubicin resistance caused by CrkL siRNA on K562/ADR cells.
JOURNAL OF CLINICAL LABORATORY ANALYSIS
(2021)
Review
Oncology
Francesco Tamiro, Andrew P. Weng, Vincenzo Giambra
Summary: Leukemia-initiating cells (LIC) are unique cells in different types of leukemia that have self-renewing capabilities and produce tumors, which are functionally distinct from bulk leukemia cells. Current conventional treatments are not effective in eliminating LICs, hence innovative therapeutics targeting LICs hold promise for developing an effective cure for ALL.
Article
Immunology
Lakshmi Sandhow, Huan Cai, Elory Leonard, Pingnan Xiao, Luana Tomaipitinca, Alma Mansson, Makoto Kondo, Xiaoyan Sun, Anne-Sofie Johansson, Karl Tryggvason, Maria Kasper, Marcus Jaras, Hong Qian
Summary: This study demonstrates the regenerative capacity of AML cells infiltrated in the skin and the role of skin mesenchymal niches in maintaining and protecting AML cells. It provides new insight into the pathology of leukemia cutis and suggests potential implications for AML relapse.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Pharmacology & Pharmacy
An-Ni Zhong, Yi Yin, Bing-Jie Tang, Lei Chen, Hong-Wei Shen, Zhi-Ping Tan, Wen-Qun Li, Qun He, Bao Sun, Yan Zhu, Jie Xiao, Zhi-Ping Jiang, Ping Xu
Summary: The study revealed that hsa_circ_0058493 was significantly overexpressed in PBMCs of CML patients and associated with poor clinical efficacy of imatinib. Silencing this circRNA significantly inhibited the development of imatinib-resistant CML cells, suggesting its potential as a therapeutic target.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Oncology
Daniel Cacic, Hakon Reikvam, Oddmund Nordgard, Peter Meyer, Tor Hervig
Summary: The study demonstrates that platelet microparticles can alter the behavior and activity of THP-1 cells, contributing to the development of acute myelogenous leukemia and resistance to chemotherapy. This finding highlights the potential role of platelet microparticles as a target for treatment in leukemia cases.
Article
Biotechnology & Applied Microbiology
Chi-Yang Tseng, Yu-Hsuan Fu, Da-Liang Ou, Jeng-Wei Lu, Hsin-An Hou, Liang-In Lin
Summary: Omipalisib exhibits anti-tumor effects in acute myeloid leukemia (AML) cells by inhibiting PI3K/AKT/mTOR signaling, suppressing mitochondrial respiration and biogenesis, and modulating metabolite levels.
CANCER GENE THERAPY
(2023)
Article
Cell Biology
Margot S. F. Roeten, Johan van Meerloo, Zinia J. Kwidama, Giovanna ter Huizen, Wouter H. Segerink, Sonja Zweegman, Gertjan J. L. Kaspers, Gerrit Jansen, Jacqueline Cloos
Summary: Ixazomib (IXA) is a promising orally available proteasome inhibitor with improved safety profile compared to Bortezomib (BTZ). In vitro and ex vivo studies showed that IXA has a similar mechanism of action as BTZ, but demonstrated anti-leukemic effects in primary leukemia cells, suggesting further pre-clinical evaluation.
Article
Multidisciplinary Sciences
Katerina Hlozkova, Ivana Hermanova, Lucie Safrhansova, Natividad Alquezar-Artieda, Daniela Kuzilkova, Adela Vavrova, Kristyna Sperkova, Marketa Zaliova, Jan Stary, Jan Trka, Julia Starkova
Summary: In this study, the relationship among PTEN deletion, ASNase sensitivity, and glucose metabolism in T-ALL cells was investigated. It was found that aberrant PTEN/PI3K/Akt signaling may contribute to the therapeutic challenge of T-ALL. Furthermore, pharmacological inhibition of Akt can enhance the sensitivity of T-ALL cells to ASNase, providing a promising therapeutic option for T-ALL patients.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Jing Cui, Yao Guo, Heshui Wu, Jiongxin Xiong, Tao Peng
Summary: The study found that everolimus (Evr) can overcome gemcitabine (GEM) resistance in pancreatic cancer by inhibiting aerobic glycolysis and promoting apoptosis. The therapeutic effect of Evr in GEM-resistant cells was significantly better than in GEM-sensitive cells.
MOLECULAR MEDICINE
(2021)
Article
Oncology
Jiachun Song, Longting Du, Ping Liu, Fuhui Wang, Bo Zhang, Yinyin Xie, Jing Lu, Yi Jin, Yan Zhou, Gang Lv, Jianmin Zhang, Saijuan Chen, Zhu Chen, Xiaojian Sun, Yuanliang Zhang, Qiuhua Huang
Summary: This study identified two cell subsets enriched for LICs in murine Setd2(-/-)-AML and disclosed the transcriptional and functional heterogeneity of LICs, revealing that the coexistence of different types of LICs in this model brings about diverse drug response.
CANCER COMMUNICATIONS
(2021)
Article
Oncology
Weixin Lai, Xinyu Li, Qian Kong, Han Chen, Yunyao Li, Lu-Hong Xu, Jianpei Fang
Summary: The study revealed that HMGB1/RAGE play a crucial role in drug resistance by regulating autophagy and apoptosis, and promoting the expression of drug efflux proteins like P-gp and MRP after chemotherapy in acute leukemia. Blocking the HMGB1/RAGE axis may be a promising therapeutic target for AL, particularly for patients with refractory or relapsed disease.
CANCER CELL INTERNATIONAL
(2021)
Article
Biology
Hae J. Park, Mark A. Gregory, Vadym Zaberezhnyy, Andrew Goodspeed, Craig T. Jordan, Jeffrey S. Kieft, James DeGregori
Summary: The bone marrow microenvironment provides protection to AML cells from FLT3 inhibitor drugs through the activation of ATM and upregulation of oxidative phosphorylation. Combination therapy with the mTOR inhibitor everolimus and the FLT3 inhibitor quizartinib effectively reduces tumor burden and prevents relapse in AML xenograft models.
Article
Biochemistry & Molecular Biology
Jakub Szymczyk, Aleksandra Czyrek, Jacek Otlewski, Malgorzata Zakrzewska
Summary: Breast cancer is a complex disease with abnormal signaling pathways that promote tumor growth. Drug resistance and reduced response to therapies are persistent challenges. Dysregulation of growth factors such as FGFs and EGF contribute to reduced treatment response. Our study highlights the role of FGFs and their receptors in promoting drug resistance in breast cancer.
Article
Cell Biology
Rui Sun, Lixiazi He, Hyeyoon Lee, Andrey Glinka, Carolin Andresen, Daniel Huebschmann, Irmela Jeremias, Karin Mueller-Decker, Caroline Pabst, Christof Niehrs
Summary: RSPO2 promotes self-renewal of AML cells and may serve as a marker for poor prognosis. It maintains AML self-renewal independently of WNT by inhibiting BMP receptor signaling.
Article
Cell Biology
Vivian Morris, Dahai Wang, Zhiheng Li, William Marion, Travis Hughes, Patricia Sousa, Taku Harada, Shannan Ho Sui, Sergey Naumenko, Jeremie Kalfon, Prerana Sensharma, Marcelo Falchetti, Renan Vinicius da Silva, Tito Candelli, Pauline Schneider, Thanasis Margaritis, Frank C. P. Holstege, Yana Pikman, Marian Harris, Ronald W. Stam, Stuart H. Orkin, Angela N. Koehler, Alex K. Shalek, Trista E. North, Maxim Pimkin, George Q. Daley, Edroaldo Lummertz da Rocha, R. Grant Rowe
Summary: This study investigates LICs in MLL-rearranged B-ALL using single-cell transcriptomics and quantitative xenotransplantation. Compared to AML, MLL-r B-ALL has abundant engraftable LICs that can replenish leukemic cellular diversity. Inhibiting oxidative phosphorylation promotes LIC emergence, while inhibiting hypoxia and glycolysis impairs MLL-r B-ALL LICs.
Review
Oncology
Alberto M. Martelli, Camilla Evangelisti, Francesca Paganelli, Francesca Chiarini, James A. McCubrey
Summary: GSK-3 consists of two isoforms, alpha and beta, that are constitutively active but can be inactivated through phosphorylation by upstream kinases. It was initially considered a tumor suppressor, but it has also been found to have oncogenic properties in promoting pathways critical for cancer cell proliferation, survival, and drug-resistance.
Review
Oncology
Salvatore Nicola Bertuccio, Laura Anselmi, Riccardo Masetti, Annalisa Lonetti, Sara Cerasi, Sara Polidori, Salvatore Serravalle, Andrea Pession
Summary: Despite improvements in therapeutic protocols and risk stratification, AML remains a major cause of childhood leukemic mortality, with high rates of relapse and poor response to conventional chemotherapy in pediatric patients. Research focuses on the genetic heterogeneity of pediatric AML, its association with clonal evolution leading to relapse, and innovative tools for enhanced diagnosis and drug screening. The ultimate goal is targeted therapy to improve prognosis and reduce toxic side effects of current treatments for pediatric AML.
Review
Cell Biology
Dania Hajka, Bartosz Budziak, Lukasz Pietras, Przemyslaw Duda, James A. McCubrey, Agnieszka Gizak
Summary: GSK3, initially identified as a critical protein in energy metabolism, is a multi-tasking kinase that links numerous signaling pathways in a cell and plays a vital role in regulating various aspects of cellular physiology. It influences processes of cell polarization, interaction with the extracellular matrix, and directional migration of cells and organelles during growth and development in an animal organism.
Review
Biochemistry & Molecular Biology
Camilla Evangelisti, Isabella Rusciano, Sara Mongiorgi, Giulia Ramazzotti, Giovanna Lattanzi, Lucia Manzoli, Lucio Cocco, Stefano Ratti
Summary: B-type lamins are essential components of the nuclear lamina and play key roles in nuclear functions, cellular processes, and organogenesis. Mutations or fluctuations in their expression levels are critical for the onset of various diseases.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Cell Biology
Stefano Ratti, Isabella Rusciano, Sara Mongiorgi, Irene Neri, Alessandra Cappellini, Pietro Cortelli, Pann-Ghill Suh, James A. McCubrey, Lucia Manzoli, Lucio Cocco, Giulia Ramazzotti
Summary: The overexpression of Lamin B1 in ADLD astrocytes affects cell survival signaling pathways, reduces astrocyte survival, and disrupts cell proliferation and cycle progression, leading to apoptosis. Additionally, it triggers a tentative activation of survival pathways that are ineffective.
Article
Biochemistry & Molecular Biology
James Andrew McCubrey, Stephen L. Abrams, Linda S. Steelman, Lucio Cocco, Stefano Ratti, Alberto M. Martelli, Paolo Lombardi, Agnieszka Gizak, Przemyslaw Duda
Summary: The study indicates that TP53 reactivator APR-246 can increase the therapeutic potential of many modified berberine compounds, which is of significance for pancreatic ductal adenocarcinoma.
Article
Cell Biology
Francesca Chiarini, Francesca Paganelli, Tommaso Balestra, Cristina Capanni, Antonietta Fazio, Maria Cristina Manara, Lorena Landuzzi, Stefania Petrini, Camilla Evangelisti, Pier-Luigi Lollini, Alberto M. Martelli, Giovanna Lattanzi, Katia Scotlandi
Summary: Lamin A plays a significant role in Ewing Sarcoma by affecting cell migration and invasiveness. Low expression of Lamin A is associated with increased aggressiveness and metastatic load in patients. This effect is linked to altered nuclear envelope proteins and increased nuclear retention of YAP/TAZ. Overexpression of Lamin A or pharmacological modulation of its maturation can prevent cell invasiveness and improve therapeutic strategies for Ewing Sarcoma.
CELL DEATH & DISEASE
(2022)
Review
Cell Biology
Alberto M. Martelli, Francesca Paganelli, Camilla Evangelisti, Francesca Chiarini, James A. McCubrey
Summary: GSK-3 is a multifunctional protein kinase involved in various physiological processes and plays a crucial role in cancer cell pathobiology. While often inactivated in cancer cells, GSK-3 isoforms can also act as tumor promoters in certain contexts.
Article
Cell Biology
Stephen L. Abrams, Przemyslaw Duda, Shaw M. Akula, Linda S. Steelman, Matilde L. Follo, Lucio Cocco, Stefano Ratti, Alberto M. Martelli, Giuseppe Montalto, Maria Rita Emma, Melchiorre Cervello, Dariusz Rakus, Agnieszka Gizak, James A. McCubrey
Summary: TP53 mutation is common in pancreatic cancer and promotes tumor growth and metastasis. APR-246, a molecule that restores wildtype TP53 function, can increase the sensitivity of PDAC cells to chemotherapy. Introduction of WT-TP53 enhances sensitivity to TP53 reactivators, chemotherapeutic drugs, and signal transduction inhibitors in PDAC cells.
Article
Chemistry, Medicinal
Manuela Labbozzetta, Paola Poma, Marco Tutone, James A. McCubrey, Maurizio Sajeva, Monica Notarbartolo
Summary: Drug resistance in cancer therapy is a major problem, involving multiple factors. This study found that the compounds phytol and heptacosane from Euphorbia intisy essential oil can improve P-gp-mediated drug transport and reverse drug resistance in tumor cells.
Review
Cell Biology
James A. McCubrey, Li Yang, Stephen L. Abrams, Linda S. Steelman, Matilde Y. Follo, Lucio Cocco, Stefano Ratti, Alberto M. Martelli, Giuseppa Augello, Melchiorre Cervello
Summary: This review discusses the roles of TP53 and miRs in the PDAC tumor microenvironment and how mutated TP53 and loss of miR expression contribute to tumor progression.
Review
Biochemistry & Molecular Biology
Alberto M. M. Martelli, Francesca Paganelli, Serena Truocchio, Carla Palumbo, Francesca Chiarini, James A. A. McCubrey
Summary: The Hedgehog (HH) signaling network is an important regulator of embryonic development. However, abnormal activation of HH signaling has been found in various malignant disorders, promoting proliferation, survival, and therapeutic resistance of neoplastic cells. In this review, the biological roles and pathophysiology of the HH pathway in normal T-cell lymphopoiesis and T-ALL are summarized, along with potential therapeutic strategies to target the HH pathway in T-ALL.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Cesare Rossi, Sherin Ramadan, Cecilia Evangelisti, Simona Ferrari, Maria Accadia, Reha M. Toydemir, Emanuele Panza
Summary: In this study, a novel pathogenetic variant affecting splicing in the CHD7 gene, c.5607+17A > G, was identified. Through the construction of minigenes using exon trapping vectors, the molecular effect of the variant on CHD7 gene splicing was characterized. The findings were confirmed using cDNA synthesized from RNA extracted from patient lymphocytes, and the alteration of splicing was shown to be due to the generation of a recognition motif for the recruitment of a splicing effector.
FRONTIERS IN GENETICS
(2023)
Review
Biochemistry & Molecular Biology
Maria Vittoria Marvi, Irene Neri, Camilla Evangelisti, Giulia Ramazzotti, Sofia Asioli, Matteo Zoli, Diego Mazzatenta, Niccolo Neri, Luca Morandi, Caterina Tonon, Raffaele Lodi, Enrico Franceschi, James A. McCubrey, Pann-Ghill Suh, Lucia Manzoli, Stefano Ratti
Summary: Phospholipases are crucial enzymes that hydrolyze phospholipids, the most abundant species in the biological membranes of healthy human brain cells. They generate lipid mediators that play essential roles in intra- and inter-cellular signaling, regulating various cellular mechanisms involved in tumor progression and aggressiveness.