Article
Oncology
Yun Xu, Ziting Wang, Lei Zhang, Congying Gao, Fahui Li, Xueming Li, Yu Ke, Hong-Min Liu, Zhenbo Hu, Liuya Wei, Zhe-Sheng Chen
Summary: The compound JOA can inhibit the proliferation of chronic myeloid leukemia cells, including those with the BCR-ABL-T315I mutation, and induce cell differentiation. This effect may be mediated by the inhibition of the BCR-ABL/c-MYC signaling pathway. JOA shows potential as a lead compound for overcoming imatinib resistance in CML therapy.
Article
Chemistry, Multidisciplinary
Bohan Ma, Hui Feng, Chao Feng, Yi Liu, Hailing Zhang, Jincheng Wang, Wenjuan Wang, Pengcheng He, Fan Niu
Summary: The study designed a dual-targeting proteolysis-targeting chimera (PROTAC) type drug that can induce Bcr/Abl degradation and activate the p53 pathway simultaneously, potentially overcoming drug resistance in Ph+ leukemias.
Article
Biochemistry & Molecular Biology
Elena V. Koroleva, Yuri V. Kornoushenko, Anna D. Karpenko, Ivan P. Bosko, Julia V. Siniutsich, Zhanna V. Ignatovich, Alexander M. Andrianov
Summary: An integrated computational approach was used to identify potential inhibitors of Bcr-Abl tyrosine kinase, an enzyme involved in chronic myeloid leukemia. Five compounds were found to effectively block the enzyme activity and exhibit high binding affinity comparable to FDA-approved kinase inhibitors. These compounds may serve as good scaffolds for the design of novel anticancer agents.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Multidisciplinary Sciences
H. Jonathan G. Lindstrom, Ran Friedman
Summary: Targeted therapies for CML are effective but rarely curative. Drug resistance is a major cause of death in CML, and preventing resistance is crucial. Drug rotation has been theorized as a way to delay resistance, and in vitro testing has shown some promising results in a CML cell line.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Medicinal
Haixia Liu, Xinyu Ding, Linyi Liu, Qianglong Mi, Quanju Zhao, Yubao Shao, Chaowei Ren, Jinju Chen, Ying Kong, Xing Qiu, Nicola Elvassore, Xiaobao Yang, Qianqian Yin, Biao Jiang
Summary: Protein degradation through CRBN-recruiting PROTACs has shown promising potential in targeting oncogenic fusion protein BCR-ABL, providing a potential therapeutic strategy for chronic myeloid leukemia.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Yonglan Liu, Mingzhen Zhang, Chung-Jung Tsai, Hyunbum Jang, Ruth Nussinov
Summary: Researchers have used extensive molecular dynamics simulations to decipher the activation and autoinhibition mechanism of c-Abl. The myristoyl group serves as a switch for c-Abl inhibition/activation, and precise SH2/N-lobe interaction is required for full activation. Bcr-Abl allosteric drugs mimic the endogenous myristoyl-mediated autoinhibition state and alter the active-site conformation, affecting the action of ATP-competitive drugs.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Plant Sciences
Xiaoying Lan, Min Hu, Liling Jiang, Jiamin Wang, Yi Meng, Xinmei Chen, Aochu Liu, Wa Ding, Haichuan Zhang, Huan Zhou, Bingyuan Liu, Guanjie Peng, Siyan Liao, Xin Chen, Jinbao Liu, Xianping Shi
Summary: The natural substance piperlongumine from the herbal medicine Piper longum L. has been found to overcome imatinib resistance in chronic myelogenous leukemia (CML), providing a new therapeutic strategy.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Tingting Lu, Jiangyan Cao, Fengming Zou, Xixiang Li, Aoli Wang, Wenliang Wang, Huamin Liang, Qingwang Liu, Chen Hu, Cheng Chen, Zhenquan Hu, Wenchao Wang, Lili Li, Jian Ge, Yang Shen, Tao Ren, Jing Liu, Ruixiang Xia, Qingsong Liu
Summary: CHMFL-48 is a novel type II kinase inhibitor that potently inhibits the wild-type BCR-ABL kinase and a panel of imatinib-resistant mutants. This drug shows strong inhibitory activity in a cellular context, blocking autophosphorylation of BCR-ABL kinase, affecting downstream signaling mediators, and inducing cell cycle progression blockade and apoptosis.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Chemistry, Physical
Abhijit Kantankar, Y. Jayaprakash Rao, G. Mallikarjun, Y. Hemasri, Raghava Reddy Kethiri
Summary: A new series of pyrimidine based chromone hybrids were synthesized and evaluated for their anti-cancer activity, showing potent effects against A549, HeLa, and K562 cancer cell lines while maintaining relative non-toxicity against normal cell lines. The selectivity of these compounds against K562 cell line was confirmed using molecular docking analysis.
JOURNAL OF MOLECULAR STRUCTURE
(2021)
Article
Immunology
Anila Vadakumchery, Hemin Faraidun, Omar El Ayoubi, Issame Outaleb, Vera Schmid, Hend Abdelrasoul, Timm Amendt, Ahmad Khadour, Corinna Setz, Katharina Goehring, Karoline Lodd, Christoffer Hitzing, Alabbas Alkhatib, Mayas Bilal, Julian Benckendorff, Abdul Kader Al Shugri, Cord Herbert Brakebusch, Niklas Engels, Moumita Datta, Elias Hobeika, Ameera Alsadeq, Hassan Jumaa
Summary: The adaptor protein SLP65 controls the down-regulation of PI3K signaling in B cells by inducing the activity of small GTPase RHOA, which activates the negative regulator PTEN. RHOA plays a unique role in B cell generation and selection, and blocking its function offers potential for treating B cell malignancies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Liling Jiang, Qingyan He, Xin Chen, Aochu Liu, Wa Ding, Haichuan Zhang, Xinmei Chen, Huan Zhou, Yi Meng, Bingyuan Liu, Guanjie Peng, Chunyan Wang, Jinbao Liu, Xianping Shi
Summary: This study found that the proteasomal deubiquitinases USP14 and UCHL5 were overexpressed in primary cancer cells from CML patients. The inhibitor of USP14 and UCHL5, b-AP15, displayed potent tumor-killing activity in BCR-ABL(WT) and BCR-ABL(T315I) CML cell lines, as well as in CML xenografts and primary CML cells. Inhibition of USP14 and UCHL5, either pharmacologically or genetically, induced cell apoptosis and decreased the protein level of BCR-ABL in CML cells expressing BCR-ABL(WT) and BCR-ABL(T315I). Moreover, b-AP15 synergistically enhanced the cytotoxic effect of TKI imatinib in BCR-ABL(WT) and BCR-ABL(T315I) CML cells.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Article
Genetics & Heredity
Aditya Singh, Prateek Bhatia
Summary: The CRISPR system successfully reduced the expression of downstream genes related to the BCR-ABL kinase signal and significantly decreased cell viability. Time-dependent kinetics revealed a long-lasting in-vitro suppressive activity of CRISPR.
CURRENT GENE THERAPY
(2021)
Article
Medicine, Research & Experimental
Jianming Wang, Yang Liang, Yuefeng Qin, Guoyun Jiang, Yuhang Peng, Wenli Feng
Summary: This study uncovers that circCRKL is specifically expressed and regulates the expression level of BCR-ABL via decoying miR-877-5p in BCR-ABL(+) cells. The findings suggest that targeting circCRKL along with imatinib treatment could be a potential therapeutic strategy for CML patients.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Oncology
Yan Yu, Zhao Zeng, Jundan Xie, Qiongyu Lu, Wenzhi Cai, Ruixi Zhang, Jinlan Pan, Yun Zhao, Aining Sun, Huiying Qiu, Suning Chen
Summary: The PAX5-UBE2D4 fusion gene identified in a case of Ph-positive mixed phenotype acute leukemia has partial oncogenic activity, promoting tumor growth and cell proliferation.
FRONTIERS IN ONCOLOGY
(2021)
Article
Cell Biology
Ting-Ting Huang, Xin Wang, Shao-Jia Qiang, Zhen-Nan Zhao, Zhuo-Xun Wu, Charles R. Ashby, Jia-Zhong Li, Zhe-Sheng Chen
Summary: The study identified a potential BCR-ABL inhibitor, ZINC21710815, through drug design and screening, which effectively inhibited the proliferation of different types of leukemia cells, inducing cell cycle arrest and apoptosis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Kendra L. Sweet, Jorge E. Cortes, Jane F. Apperley, Mel Mann, Michael J. Mauro, Vivian G. Oehler, Cristina Ruiz, Charles A. Schiffer, Lori A. Ehrlich, Gulsum E. Pamuk, Joseph Wynne, Gautam U. Mehta, R. Angelo de Claro, Marc R. Theoret, B. Douglas Smith, Kelly J. Norsworthy
Summary: The FDA has an accelerated approval program for potentially promising drugs in treating serious conditions. All available treatments for chronic myeloid leukemia (CML) have undergone this program. A group consisting of CML experts, patient panelists, and FDA members gathered to discuss the utility of the accelerated approval program in CML and its future role in drug development, and the results are summarized here.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Jorge E. Cortes, Andreas Hochhaus, Naoto Takahashi, Richard A. Larson, Ghayas C. Issa, Felice Bombaci, Nicholas Ramscar, Sophie Ifrah, Timothy P. Hughes
Summary: Asciminib, a BCR-ABL1 inhibitor that works through the STAMP mechanism, has shown favorable efficacy and safety in patients with chronic myeloid leukemia in chronic phase. The ongoing ASC4FIRST trial aims to compare the effectiveness of Asciminib with investigator-selected TKIs in newly diagnosed patients with chronic myeloid leukemia.
Article
Oncology
Andreas Hochhaus, Delphine Rea, Carla Boquimpani, Yosuke Minami, Jorge E. Cortes, Timothy P. Hughes, Jane F. Apperley, Elza Lomaia, Sergey Voloshin, Anna Turkina, Dong-Wook Kim, Andre Abdo, Laura Maria Fogliatto, Philipp le Coutre, Koji Sasaki, Dennis Dong Hwan Kim, Susanne Saussele, Mario Annunziata, Naeem Chaudhri, Lynette Chee, Valentin Garcia-Gutierrez, Shruti Kapoor, Alex Allepuz, Sara Quenet, Veronique Bedoucha, Michael J. Mauro
Summary: Asciminib, a BCR-ABL1 inhibitor that targets the ABL Myristoyl Pocket (STAMP), is approved worldwide for the treatment of adults with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (CML-CP) who have been previously treated with at least 2 tyrosine kinase inhibitors (TKIs). In the ASCEMBL study, asciminib demonstrated superior efficacy and better safety and tolerability compared to bosutinib in patients with CML-CP who had received at least 2 prior TKIs. The major molecular response rate at week 96 was significantly higher with asciminib than with bosutinib, and fewer adverse events and treatment discontinuations were observed with asciminib.
Article
Urology & Nephrology
Camilo Montero, Nancy Yomayusa, Rodolfo Torres, Jorge Cortes, Carlos Alvarez, Juan Gallo, Guillermo Aldana, Andres Acevedo, Maria Rios, Johana Echeverri, Zuly Yepes, Adriana Silva, Diana Gayon, Jorge Perez, Milciades Ibanez
Summary: This study aimed to evaluate asymptomatic CMV reactivation and CMV disease in kidney transplant recipients with positive CMV serostatus. The results showed that asymptomatic CMV reactivation was higher in patients who received thymoglobulin induction, while the rates of CMV disease were similar between the two treatment groups. The significant difference in asymptomatic CMV reactivation between the two groups did not affect graft function and histology.
Article
Oncology
Michael J. Mauro, Timothy P. Hughes, Dong-Wook Kim, Delphine Rea, Jorge E. Cortes, Andreas Hochhaus, Koji Sasaki, Massimo Breccia, Moshe Talpaz, Oliver Ottmann, Hironobu Minami, Yeow Tee Goh, Daniel J. DeAngelo, Michael C. Heinrich, Valle Gomez-Garcia de Soria, Philipp le Coutre, Francois-Xavier Mahon, Jeroen J. W. M. Janssen, Michael Deininger, Naranie Shanmuganathan, Mark B. Geyer, Silvia Cacciatore, Fotis Polydoros, Nithya Agrawal, Matthias Hoch, Fabian Lang
Summary: Asciminib has been approved for patients with Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia (CML-CP) who have received >= 2 prior tyrosine kinase inhibitors or have the T315I mutation. A phase 1 trial evaluated the safety and efficacy of asciminib monotherapy in 115 CML-CP patients without T315I. After a median exposure of approximately 4 years, most patients remained on asciminib and achieved significant molecular responses.
Article
Oncology
Fabio Efficace, Francesco Cottone, Betina Yanez, Vamsi Kota, Fausto Castagnetti, Giovanni Caocci, Massimiliano Bonifacio, Andrea Patriarca, Isabella Capodanno, Maria Cristina Miggiano, Mario Tiribelli, Massimo Breccia, Luigia Luciano, Valentina Giai, Alessandra Iurlo, Elisabetta Abruzzese, Carmen Fava, Shira Dinner, Jessica K. Altman, Gianantonio Rosti, Jorge Cortes, Marco Vignetti, David Cella
Summary: Patient-reported symptom monitoring from the beginning of therapy in patients with CML may be critical to improve adherence to therapy and early molecular response rates. The current findings suggest that systematic monitoring of patient-reported symptoms is associated with high adherence rates.
Article
Oncology
Koji Sasaki, Kiyomi Morita, Hagop Kantarjian, Guillermo Garcia-Manero, Elias Jabbour, Farhad Ravandi, Marina Konopleva, Gautam Borthakur, William Wierda, Naval Daver, Koichi Takahashi, Courtney Dinardo, Guillermo Montalban Bravo, Ghayas C. Issa, Sherry A. Pierce, Kelly A. Soltysiak, Martha S. Tingen, Jorge E. Cortes
Summary: This study investigated the impact of geographic disparities on cancer survival. The study found that factors such as age, income, race, and distance to cancer centers were predictive of survival. The results showed significant disparities in cancer care based on geographic locations.
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Article
Virology
Pankaj Ahluwalia, Ashutosh Vashisht, Harmanpreet Singh, Nikhil Shri Sahajpal, Ashis K. Mondal, Kimya Jones, Jaspreet Farmaha, Ryan Bloomquist, Caroline Marie Carlock, Drew Fransoso, Christina Sun, Tyler Day, Comfort Prah, Trinh Vuong, Patty Ray, Danielle Bradshaw, Marisol Miranda Galvis, Sadanand Fulzele, Girindra Raval, Justin Xavier Moore, Jorge Cortes, Jeffrey N. James, Vamsi Kota, Ravindra Kolhe
Summary: This study aimed to investigate the temporal changes in the humoral immune response among healthcare workers in Augusta, GA, USA, and explore any associations with ethno-demographic features. The findings showed a significant decline in neutralizing antibody (NAb) and IgG levels at 8-12 months post-vaccination, with a more pronounced decline in White HCWs. Booster doses were found to increase antibody levels significantly, while participants without booster doses experienced a decline in antibody levels at 12 months post-vaccination.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Review
Hematology
Mahesh Swaminathan, Jorge E. E. Cortes
Summary: Gemtuzumab-ozogamicin (GO) is an ADC approved for the treatment of CD33(+) AML. Despite initial recall due to lack of efficacy and hepatotoxicities, subsequent phase 3 studies showed significant survival benefits with lower and fractionated doses of GO in combination with standard chemotherapy. GO at a dose of 6 mg/m(2) was associated with higher grade > 3 hepatotoxicities and VOD compared to 3 mg/m(2). GO has been reapproved in 2017 and is currently being studied for its role in combination therapies and MRD elimination in CD33(+) AML patients.
THERAPEUTIC ADVANCES IN HEMATOLOGY
(2023)
Meeting Abstract
Hematology
Gemma Shay, Michael W. Deininger, Tim H. Bruemmendorf, Jeffrey H. Lipton, Leif Stenke, Eric Leip, Simon Purcell, Andrea Viqueira, Jorge E. Cortes
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Meeting Abstract
Oncology
Richard F. Schlenk, Pau Montesinos, Antonio Romero-Aguilar, Radovan Vrhovac, Elzbieta Patkowska, Hee-Je Kim, Pavel Zak, Po-Nan Wang, James Hanyok, Li Liu, Yasser Mostafa Kamel, Arnaud Lesegretain, Jorge Cortes, Mikkael A. Sekeres, Herve Dombret, Sergio Amadori, Jianxiang Wang, Alexander E. Perl, Mark J. Levis, Harry P. Erba
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Meeting Abstract
Oncology
Muhannad Sharara, Kellen Cristine Tjioe, Marisol Miranda Galvis, Gagan Agrawal, Andrew Balas, Jorge Cortes
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Meeting Abstract
Oncology
Ana Toreli, Marisol Miranda-Galvis, Marcelo Addas-Carvalho, Eliana Miranda, Leonardo Fechio, Adriana Duarte, Audrey Basso, Gislaine Duarte, Samuel Medina, Fernando Pericole, Bruno Benites, Ravindra Kolhe, Kimya Jones, Harmanpreet Singh, Sara Teresinha Olalla Saad, Carmino Antonio de Souza, Jorge Cortes, Katia Pagnano
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Meeting Abstract
Oncology
Mark J. Levis, Harry P. Erba, Pau Montesinos, Radovan Vrhovac, Elzbieta Patkowska, Hee-Je Kim, Pavel Zak, Po-Nan Wang, Jaime E. Connolly Rohrbach, Ken C. N. Chang, James Hanyok, Li Liu, Yasser Mostafa Kamel, Arnaud Lesegretain, Jorge Cortes, Mikkael A. Sekeres, Herve Dombret, Sergio Amadori, Jianxiang Wang, Richard F. Schlenk, Alexander E. Perl
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Meeting Abstract
Oncology
Michael Mauro, Andreas Hochhaus, Timothy Hughes, Delphine Rea, Carla Boquimpani, Yosuke Minami, Jane Apperley, Valentin Garcia-Gutierrez, Shruti Kapoor, Noemi Espurz, Vishal Dhamal, Jorge Cortes
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)