Mutation status and clinical outcome of 89 imatinib mesylate-resistant chronic myelogenous leukemia patients: a retrospective analysis from the French intergroup of CML (Fi(phi)-LMC GROUP)

Leukemia
F E NicoliniCatherine Roche-Lestienne

Abstract

The emergence of ABL point mutations is the most frequent cause for imatinib resistance in chronic myelogenous leukemia (CML) patients and can occur during any phase of the disease; however, their clinical impact remains controversial. In this study, we retrospectively analyzed the predictive impact of 94 BCR-ABL kinase domain mutations (18 T315I, 26 P-loop, 50 in other sites) found in 89 imatinib-resistant CML patients. At imatinib onset, 64% of patients (57/89) were in chronic phase (CP), 24% (21/89) in accelerated phase (AP) and 12% (11/89) in blastic phase (BP). T315I and P-loop mutations were preferentially discovered in accelerated phase of BP CML, and other types of mutations in CP (P=0.003). With a median follow-up of 39.2 months (6.3-67.2), since imatinib initiation, overall survival (OS) was significantly worse for P-loop (28.3 months) and for T315I (12.6 months), and not reached for other mutations (P=0.0004). For CP only, multivariate analysis demonstrated a worse OS for P-loop mutations (P=0.014), and a worse progression-free survival (PFS) for T315I mutations (P=0.014). Therefore, P-loop and T315I mutations selectively impair the outcome of imatinib-resistant CML patients, in contrast to other mutations, which may...Continue Reading

References

Aug 9, 1996·The Journal of Biological Chemistry·P B Allen, L M Wiedemann
Aug 1, 2002·Proceedings of the National Academy of Sciences of the United States of America·Sergei RoumiantsevRichard A Van Etten
Feb 8, 2003·The Lancet Oncology·Carlo B Gambacorti-PasseriniLeonardo Scapozza
Mar 15, 2003·The New England Journal of Medicine·Stephen G O'BrienUNKNOWN IRIS Investigators
Dec 17, 2003·Current Opinion in Hematology·Valentina NardiGeorge Q Daley
Jan 28, 2004·The Hematology Journal : the Official Journal of the European Haematology Association·Haifa-Kathrin Al-AliMichael Werner Nikolaus Deininger
Jun 15, 2004·Biochemical and Biophysical Research Communications·Masahide YamamotoOsamu Miura
Jul 24, 2004·Hematology/oncology Clinics of North America·Andreas Hochhaus, Timothy Hughes

❮ Previous
Next ❯

Citations

Apr 29, 2010·Current Hematologic Malignancy Reports·Meetu AgrawalAlfonso Quintás-Cardama
Jul 24, 2007·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Pin-Pen HsiehChung-Che Chang
Aug 6, 2008·The Pharmacogenomics Journal·O N Ikediobi
Nov 30, 2012·The New England Journal of Medicine·Jorge E CortesMoshe Talpaz
Nov 5, 2013·The New England Journal of Medicine·J E CortesUNKNOWN PACE Investigators
Nov 29, 2007·Current Opinion in Oncology·Dragana Milojkovic, Jane Apperley
Apr 15, 2010·Molecular Cancer Therapeutics·Fei FeiNora Heisterkamp
Dec 17, 2008·Hematology·Junia V Melo, Charles Chuah
Oct 3, 2008·Journal of Hematology & Oncology·Shundong Cang, Delong Liu
Nov 27, 2010·Journal of Hematology & Oncology·Guoqing WeiDelong Liu
Aug 10, 2010·Core Evidence·Elias JabbourHagop Kantarjian
Nov 19, 2009·Drug Design, Development and Therapy·Carmen FavaElias Jabbour
Jan 1, 2009·OncoTargets and Therapy·Ila Tamascar, Jeyanthi Ramanarayanan
Mar 28, 2008·Proceedings of the National Academy of Sciences of the United States of America·Thomas O'HareMichael W Deininger
Apr 7, 2010·Leukemia & Lymphoma·Pratibha SharmaLalit Kumar
Feb 9, 2011·Leukemia & Lymphoma·Joana M Diamond, Junia V Melo
Mar 21, 2012·Expert Opinion on Pharmacotherapy·Maria Florencia TanakaElias Jabbour
Dec 22, 2007·Expert Review of Anticancer Therapy·Elias JabbourHagop M Kantarjian
Feb 1, 2009·Expert Review of Hematology·Kimmo PorkkaBengt Simonsson
Jul 24, 2013·Expert Opinion on Pharmacotherapy·Aziz NazhaAlfonso Quintás-Cardama
Jun 14, 2008·Expert Opinion on Investigational Drugs·Elias JabbourHagop Kantarjian
Aug 20, 2015·Cancer Investigation·Katia Borgia Barbosa PagnanoRaquel M Bengió

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.