Article
Hematology
Jorge Cortes, Jane Apperley, Elza Lomaia, Beatriz Moiraghi, Maria Undurraga Sutton, Carolina Pavlovsky, Charles Chuah, Tomasz Sacha, Jeffrey H. Lipton, Charles A. Schiffer, James McCloskey, Andreas Hochhaus, Philippe Rousselot, Gianantonio Rosti, Hugues de Lavallade, Anna Turkina, Christine Rojas, Christopher Kevin Arthur, Lori Maness, Moshe Talpaz, Michael Mauro, Tracey Hall, Vickie Lu, Shouryadeep Srivastava, Michael Deininger
Summary: The study focused on the treatment of CP-CML patients with different doses of ponatinib, finding that the optimal benefit/risk outcomes were achieved with a starting dose of 45 mg and decreased to 15 mg upon response.
Article
Hematology
Hagop M. Kantarjian, Elias Jabbour, Michael Deininger, Elisabetta Abruzzese, Jane Apperley, Jorge Cortes, Charles Chuah, Daniel J. DeAngelo, John DiPersio, Andreas Hochhaus, Jeffrey Lipton, Franck E. Nicolini, Javier Pinilla-Ibarz, Delphine Rea, Gianantonio Rosti, Philippe Rousselot, Neil P. Shah, Moshe Talpaz, Shouryadeep Srivastava, Xiaowei Ren, Michael Mauro
Summary: Ponatinib has demonstrated deep and durable responses in patients with chronic-phase chronic myeloid leukemia, especially in those resistant to second-generation TKI treatment, and has shown good safety and survival outcomes.
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Article
Medicine, Research & Experimental
Haidee Aranda-Tavio, Carlota Recio, Pedro Martin-Acosta, Miguel Guerra-Rodriguez, Yeray Brito-Casillas, Rosa Blanco, Vanessa Junco, Javier Leon, Juan Carlos Montero, Lucia Gandullo-Sanchez, Grant McNaughton-Smith, Juan Manuel Zapata, Atanasio Pandiella, Angel Amesty, Ana Estevez-Braun, Leandro Fernandez-Perez, Borja Guerra
Summary: JKST6 exhibits potent antitumoral activity against CML cells by modulating apoptosis signaling pathways and mitosis control, inhibiting cell proliferation. Additionally, it shows effectiveness in BCR-ABL1-positive and resistant cells, suggesting its potential as a novel multikinase modulator in CML therapy.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Pharmacology & Pharmacy
Hyacinthe Johnson-Ansah, Benjamin Maneglier, Francoise Huguet, Laurence Legros, Martine Escoffre-Barbe, Martine Gardembas, Pascale Cony-Makhoul, Valerie Coiteux, Laurent Sutton, Wajed Abarah, Camille Pouaty, Jean-Michel Pignon, Bachra Choufi, Sorin Visanica, Benedicte Deau, Laure Morisset, Emilie Cayssials, Mathieu Molimard, Stephane Bouchet, Francois-Xavier Mahon, Franck Nicolini, Philippe Aegerter, Jean-Michel Cayuela, Marc Delord, Heriberto Bruzzoni-Giovanelli, Philippe Rousselot
Summary: This study evaluated the value of therapeutic drug monitoring (TDM) in imatinib treatment for patients with chronic myelogenous leukemia. The results showed that TDM strategy significantly increased the plasma concentration of imatinib and improved the treatment outcome for patients.
Article
Multidisciplinary Sciences
Yotaro Ochi, Kenichi Yoshida, Ying-Jung Huang, Ming-Chung Kuo, Yasuhito Nannya, Ko Sasaki, Kinuko Mitani, Noriko Hosoya, Nobuhiro Hiramoto, Takayuki Ishikawa, Susan Branford, Naranie Shanmuganathan, Kazuma Ohyashiki, Naoto Takahashi, Tomoiku Takaku, Shun Tsuchiya, Nobuhiro Kanemura, Nobuhiko Nakamura, Yasunori Ueda, Satoshi Yoshihara, Rabindranath Bera, Yusuke Shiozawa, Lanying Zhao, June Takeda, Yosaku Watatani, Rurika Okuda, Hideki Makishima, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Masashi Sanada, Akifumi Takaori-Kondo, Satoru Miyano, Seishi Ogawa, Lee-Yung Shih
Summary: In chronic myeloid leukaemia (CML), the drivers of blast crisis and resistance to tyrosine kinase inhibitors are not fully characterised. Analysis of a cohort of CML samples using genomic technologies reveals that at least one driver alteration is associated with progression and worse prognosis. Genetic abnormalities can help predict clinical outcomes and guide clinical decisions in CML.
NATURE COMMUNICATIONS
(2021)
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
Hematology
Aram Bidikian, Elias Jabbour, Ghayas C. C. Issa, Nicholas J. J. Short, Koji Sasaki, Hagop Kantarjian
Summary: Achieving major molecular response (MMR) with BCR::ABL1 tyrosine kinase inhibitors (TKIs) is important in the treatment of chronic myeloid leukemia (CML). However, patients who achieve a major cytogenetic response (MCyR) within the first 2 years of TKI therapy can still have good long-term outcomes, even without achieving MMR. The value of MMR is less pronounced among older CML patients, who often face mortality due to comorbidities unrelated to CML.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Oncology
Ryan Yen, Sarah Grasedieck, Andrew Wu, Hanyang Lin, Jiechuang Su, Katharina Rothe, Helen Nakamoto, Donna L. Forrest, Connie J. Eaves, Xiaoyan Jiang
Summary: This study analyzed differentially expressed miRNAs in CML patients, showing that the combination of miR-145 and miR-708 effectively predicts response to NL in treatment-naive patients, while miR-150 and miR-185 are significant classifiers at 1 month and 3 months post-NL therapy.
Article
Cell Biology
Narissa Parry, Caroline Busch, Victoria Assmann, Jennifer Cassels, Alan Hair, G. Vignir Helgason, Helen Wheadon, Mhairi Copland
Summary: Dysregulation of the BCL-2 family is implicated in protecting CML cells, making it a viable therapeutic target. BH3 mimetics show clinical promise in the treatment of CML and can be used in combination with standard therapies. Combination of TKIs and BH3 mimetics significantly reduces cell viability and induces apoptosis in BP-CML cells. BH3 mimetics are more effective in myeloid BP-CML compared to single treatment.
CELL DEATH DISCOVERY
(2022)
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)
Review
Oncology
Kota Yoshifuji, Koji Sasaki
Summary: The prognosis of CML-CP has significantly improved with the introduction of imatinib. Besides imatinib, other TKIs and a novel drug asciminib are now available. Long-term TKI therapy requires individualized selection based on toxicity profile to minimize chronic toxicity and the risk of adverse events. This review summarizes the characteristics and adverse event profile of each TKI and discusses future perspectives in the treatment of CML-CP.
FRONTIERS IN ONCOLOGY
(2022)
Article
Pharmacology & Pharmacy
Francois Pierre Combes, Ying Fei Li, Matthias Hoch, Sebastien Lorenzo, Yu-Yun Ho, Sherwin K. B. Sy
Summary: Asciminib has potent activity against the T315I mutation in chronic myeloid leukemia patients. A longitudinal pharmacokinetic/pharmacodynamic model was developed to characterize the exposure-efficacy relationship of Asciminib. The model demonstrated the appropriateness of different doses for patients with or without the T315I mutation.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Giordana Feriotto, Federico Tagliati, Riccardo Giriolo, Fabio Casciano, Claudio Tabolacci, Simone Beninati, Mahmud Tareq Hassan Khan, Carlo Mischiati
Summary: Caffeic acid demonstrated anti-proliferative and apoptosis-inducing effects on chronic myeloid leukemia cells at micro-molar concentrations, by increasing the expression of cell cycle repressor genes. Additionally, it enhanced the anti-leukemic effect of imatinib, highlighting its nutraceutical potential in CML.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Bharathi M. Rajamani, Raveen Stephen Stallon Illangeswaran, Esther Sathya Bama Benjamin, Balaji Balakrishnan, Daniel Zechariah Paul Jebanesan, Saswati Das, Aswin Anand Pai, Rakhi Thalayattu Vidhyadharan, Ajith Mohan, Sreeja Karathedath, Aby Abraham, Vikram Mathews, Shaji R. Velayudhan, Poonkuzhali Balasubramanian
Summary: This study identified that Retinoid-X-receptor alpha (RXRA), a ligand-activated transcription factor, was downregulated in imatinib mesylate (IM)-resistant chronic myeloid leukemia (CML) cell lines and primary CML patient samples. Pre-treatment with RXRA agonists improved sensitivity to IM in vitro and reduced leukemic burden and prolonged survival in vivo. Overexpression of RXRA inhibited proliferation and improved sensitivity to IM both in vitro and in vivo. Combining IM with RXRA ligands may serve as an alternative treatment strategy for CML patients with suboptimal response to IM.
FRONTIERS IN PHARMACOLOGY
(2023)
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.
