Molecular biology of bcr-abl1-positive chronic myeloid leukemia
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TLDR
Primordial aspects of the pathogenesis of CML, such as the mechanisms responsible for the transition from chronic phase to blast crisis, the causes of genomic instability and faulty DNA repair, the phenomenon of stem cell quiescence, the role of tumor suppressors in TKI resistance and CML progression, still remain poorly understood are synthesized.About:
This article is published in Blood.The article was published on 2009-02-19 and is currently open access. It has received 617 citations till now. The article focuses on the topics: Imatinib mesylate & Chronic myelogenous leukemia.read more
Citations
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Journal ArticleDOI
Chronic Myeloid Leukemia: An Update of Concepts and Management Recommendations of European LeukemiaNet
Michele Baccarani,Jorge E. Cortes,Fabrizio Pane,Dietger Niederwieser,Giuseppe Saglio,Jane F. Apperley,Francisco Cervantes,Michael W. Deininger,Alois Gratwohl,François Guilhot,Andreas Hochhaus,Mary M. Horowitz,Timothy P. Hughes,Hagop M. Kantarjian,Richard A. Larson,Jerald P. Radich,Bengt Simonsson,Richard T. Silver,John M. Goldman,Rüdiger Hehlmann +19 more
TL;DR: Imatinib should be continued indefinitely in optimal responders and second-generation TKIs are recommended, followed by allogeneic hematopoietic stem-cell transplantation only in instances of failure and, sometimes, suboptimal response, depending on transplantation risk.
Journal ArticleDOI
Targeting neoantigens to augment antitumour immunity
TL;DR: This Review discusses the emerging evidence that neoantigens are recognized by the immune system and can be targeted to increase antitumour immunity, and provides a framework for personalized cancer immunotherapy through the identification and selective targeting of individual tumour neoantIGens.
Journal ArticleDOI
Modular PROTAC Design for the Degradation of Oncogenic BCR-ABL
Ashton C. Lai,Momar Toure,Doris Hellerschmied,Jemilat Salami,Saul Jaime-Figueroa,Ko Eunhwa,John Hines,Craig M. Crews +7 more
TL;DR: During the course of their development, it was discovered that the capacity of a PROTAC to induce degradation involves more than just target binding: the identity of the inhibitor warhead and the recruited E3 ligase largely determine the degradation profiles of the compounds.
Journal ArticleDOI
Small molecules in targeted cancer therapy: advances, challenges, and future perspectives.
Lei Zhong,Y. Li,Liang Xiong,Wen-Jing Wang,Ming Wu,Ting Yuan,Wei Yang,Chenyu Tian,Zhuang Miao,Tianqi Wang,Shengyong Yang +10 more
TL;DR: A comprehensive review of small-molecule targeted anti-cancer drugs according to the target classification is conducted, which presents all the approved drugs as well as important drug candidates in clinical trials for each target, and discusses the current challenges.
Journal ArticleDOI
Discovery of 3-[2-(imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a potent, orally active pan-inhibitor of breakpoint cluster region-abelson (BCR-ABL) kinase including the T315I gatekeeper mutant.
Wei-Sheng Huang,Chester A. Metcalf,Raji Sundaramoorthi,Yihan Wang,Dong Zou,R. Mathew Thomas,Xiaotian Zhu,Lisi Cai,David Wen,Shuangying Liu,Jan Romero,Jiwei Qi,Ingrid Chen,Geetha Banda,Scott Paul Lentini,Sasmita Das,Qihong Xu,Jeff Keats,Frank Wang,Scott Wardwell,Yaoyu Ning,Joseph Snodgrass,Marc I Broudy,Karin Russian,Tianjun Zhou,Lois Commodore,Narayana I. Narasimhan,Qurish K. Mohemmad,John Iuliucci,Victor M. Rivera,David C. Dalgarno,Tomi K. Sawyer,Tim Clackson,William C. Shakespeare +33 more
TL;DR: Daily oral administration of 20g significantly prolonged survival of mice injected intravenously with BCR-ABL(T315I) expressing Ba/F3 cells, and coupled with a favorable ADME profile, support the potential of 20G to be an effective treatment for CML, including patients refractory to all currently approved therapies.
References
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The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation.
Peter Angel,Michael Karin +1 more
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Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification
Mercedes E. Gorre,Mansoor Mohammed,Katharine Ellwood,Nicholas C. Hsu,Ron Paquette,P. Nagesh Rao,Charles L. Sawyers +6 more
TL;DR: It is found that drug resistance is associated with the reactivation of BCR-ABL signal transduction in all cases examined and a strategy for identifying inhibitors of STI-571 resistance is suggested.
Journal ArticleDOI
Activity of a Specific Inhibitor of the BCR-ABL Tyrosine Kinase in the Blast Crisis of Chronic Myeloid Leukemia and Acute Lymphoblastic Leukemia with the Philadelphia Chromosome
Brian J. Druker,Charles L. Sawyers,Hagop M. Kantarjian,Debra Resta,Sofia Fernandes Reese,John Ford,Renaud Capdeville,Moshe Talpaz +7 more
TL;DR: The BCR-ABL tyrosine kinase inhibitor STI571 is well tolerated and has substantial activity in the blast crises of CML and in Ph-positive ALL.
Journal ArticleDOI
Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome
TL;DR: It is demonstrated that P210bcr/abl expression can induce chronic myelogenous leukemia and retrovirus-mediated expression of the protein provides a murine model system for further analysis of the disease.
Journal ArticleDOI
Overriding Imatinib Resistance with a Novel ABL Kinase Inhibitor
TL;DR: BMS-354825 is an orally bioavailable ABL kinase inhibitor with two-log increased potency relative to imatinib that retains activity against 14 of 15 imatinIB-resistant BCR-ABL mutants and illustrates how molecular insight into kinase inhibitors resistance can guide the design of second-generation targeted therapies.
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