Article
Hematology
Huimin Feng, Yue Fu, Zelong Cui, Minran Zhou, Lu Zhang, Zhenxing Gao, Sai Ma, Chunyan Chen
Summary: This study shows that PHF8 is significantly increased in CML patients and inhibits cell differentiation while promoting cell proliferation. Targeting PHF8, which directly regulates BCR::ABL1 expression, may be a useful therapeutic approach for CML.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Review
Hematology
Naranie Shanmuganathan, Timothy P. Hughes
Summary: The recent approval of asciminib as a treatment option for CML patients provides clinicians with more choices for therapy. Asciminib is a highly potent BCR-ABL1 inhibitor with limited off-target effects, but its position among other available TKIs is still unclear. There are many unanswered questions about the optimal use of asciminib.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Review
Medicine, General & Internal
Jorge Cortes, Carolina Pavlovsky, Susanne Saussele
Summary: Tyrosine-kinase inhibitors have significantly altered the natural course of chronic myeloid leukaemia, allowing some patients to approach a near-normal life expectancy. Successful treatment requires understanding the patient's treatment goals, monitoring optimal response hallmarks, timely interventions, recognition of adverse events, and management of comorbidities.
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
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
Multidisciplinary Sciences
Yosuke Tanaka, Reina Takeda, Tsuyoshi Fukushima, Keiko Mikami, Shun Tsuchiya, Moe Tamura, Keito Adachi, Terumasa Umemoto, Shuhei Asada, Naoki Watanabe, Soji Morishita, Misa Imai, Masayoshi Nagata, Marito Araki, Hitoshi Takizawa, Tomofusa Fukuyama, Chrystelle Lamagna, Esteban S. Masuda, Ryoji Ito, Susumu Goyama, Norio Komatsu, Tomoiku Takaku, Toshio Kitamura
Summary: Leukemia stem cells in chronic myeloid leukemia are resistant to imatinib, but can be eliminated by combining imatinib with IRAK1/4 inhibitors that inhibit the IRAK1/4-NF-kappa B-PD-L1 signaling pathway.
NATURE COMMUNICATIONS
(2022)
Article
Hematology
Ahlam Nasser, Ally Hussein, Clara Chamba, Mbonea Yonazi, Rosemary Mushi, Anna Schuh, Lucio Luzzatto
Summary: Imatinib is the main treatment for chronic myeloid leukemia in Tanzania, but the majority of patients do not achieve deep molecular response, likely due to late diagnosis, cytopenias requiring drug interruptions, and poor treatment adherence.
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
Biochemistry & Molecular Biology
Rachid Lahlil, Anne Aries, Maurice Scrofani, Celine Zanetti, Desline Hennequin, Bernard Drenou
Summary: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disease characterized by the presence of the BCR-ABL fusion gene. Treatment with tyrosine kinase inhibitors (TKIs) such as imatinib mesylate (IM) has significantly improved clinical outcomes for CML patients, but IM resistance remains a major challenge. The cause of IM resistance in CML cells is unclear, but additional genetic alterations in leukemic stem cells (LSCs) are a common cause of relapse. A study found that a rare subpopulation of stem cells called very small embryonic-like stem cells (VSELs) in adult CML patients is resistant to IM and less sensitive to apoptosis compared to leukemic hematopoietic stem cells (HSCs). The expression levels of certain miRNAs are also affected in these IM-resistant VSELs, including miR-126 and miR-21, which are involved in LSC leukemia-initiating capacity and growth.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Zhen Liu, Wenlong Zheng, Yuan Liu, Binghe Zhou, Yuqing Zhang, Fan Wang
Summary: The study showed that HSPA8 is overexpressed in imatinib-resistant CML cells and its ablation can inhibit cell proliferation, induce autophagy, and enhance the anti-tumor activity of imatinib. These findings reveal the role of HSPA8 in IR-CML and suggest its potential as a target for treatment.
EXPERIMENTAL CELL RESEARCH
(2021)
Article
Hematology
Hjalmar Flygt, Fredrik Sandin, Torsten Dahlen, Arta Dremaine, Anna Lubking, Berit Markevarn, Kristina Myhr-Eriksson, Karin Olsson, Ulla Olsson-Stromberg, Anders Sjalander, Stina Soderlund, Lovisa Wennstrom, Hans Wadenvik, Leif Stenke, Martin Hoglund, Johan Richter
Summary: Clinical trials have shown that discontinuing TKI treatment in selected patients with CML is feasible, and this practice is common in clinical settings. The main reasons for stopping TKI treatment are achieving deep molecular response or other specific causes.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Article
Medicine, Research & Experimental
Camila Albuquerque Pinto, Adrhyann Jullyanne de Sousa Portilho, Maritza Cavalcante Barbosa, Maria Elisabete Amaral De Moraes, Jose Alexandre Rodrigues De Lemos, Rommel Mario Rodriguez Burbano, Caroline Aquino Moreira-nunes
Summary: The combined therapy of ATRA and IM showed significant decrease in BCR-ABL and ABCB1 gene expression, possibly through differentiation of blast cells. This suggests that the therapy could be effective for blast crisis and CML patients resistant to current treatments.
Article
Hematology
Barbara Peter, Gregor Eisenwort, Irina Sadovnik, Karin Bauer, Michael Willmann, Thomas Ruelicke, Daniela Berger, Gabriele Stefanzl, Georg Greiner, Gregor Hoermann, Alexandra Keller, Dominik Wolf, Martin Culen, Georg E. Winter, Thomas Hoffmann, Ana-Iris Schiefer, Wolfgang R. Sperr, Johannes Zuber, Jiri Mayer, Peter Valent
Summary: In this study, targeting BRD4 and MYC was found to sensitize CML cells against BCR::ABL1 TKI, overcoming multiple forms of drug resistance in CML LSC.
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Article
Medicine, Research & Experimental
Kinjal D. Patel, Maitri De, Disha D. Jethva, Bharati S. Rathod, Prabhudas S. Patel
Summary: This study investigated the predictive value of sialylation changes in assessing imatinib mesylate (IM) resistance in chronic myeloid leukemia (CML) cases. The results showed that alterations in TSA, ST3GAL1, and ST3GAL2 levels were associated with IM resistance, providing clinical relevance in treatment monitoring and IM resistance treatment.
ARCHIVES OF MEDICAL RESEARCH
(2022)
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
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
Hematology
Mycal Casey, Lorriane Odhiambo, Nidhi Aggarwal, Mahran Shoukier, K. M. Islam, Jorge Cortes
Summary: Despite advances in cancer outcomes, there are significant health disparities in the treatment of lymphomas. This study examined the representation of different demographic groups in randomized controlled trials (RCTs) for lymphoma and found significant underrepresentation of black, Hispanic, and female patients. Geographic distribution of trials also limited access for patients in certain areas. Correcting enrollment disparities is crucial to ensure that the results of these trials are applicable to all populations.
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)