Persistence of leukemia stem cells in chronic myelogenous leukemia patients in prolonged remission with imatinib treatment.
TLDR
It is demonstrated that BCR-ABL(+) stem cells persist in CML patients despite prolonged treatment with imatinib, and support ongoing efforts to target this population.About:
This article is published in Blood.The article was published on 2011-11-17 and is currently open access. It has received 236 citations till now. The article focuses on the topics: Imatinib mesylate & Chronic myelogenous leukemia.read more
Citations
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European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013
Michele Baccarani,Michael W. Deininger,Gianantonio Rosti,Andreas Hochhaus,Simona Soverini,Jane F. Apperley,Francisco Cervantes,Richard E. Clark,Jorge E. Cortes,François Guilhot,Henrik Hjorth-Hansen,Timothy P. Hughes,Hagop M. Kantarjian,Dong-Wook Kim,Richard A. Larson,Jeffrey H. Lipton,François Xavier Mahon,Giovanni Martinelli,Jiri Mayer,Martin C. Müller,Dietger Niederwieser,Fabrizio Pane,Jerald P. Radich,Philippe Rousselot,Giuseppe Saglio,Susanne Saußele,Charles A. Schiffer,Richard T. Silver,Bengt Simonsson,Juan Luis Steegmann,John M. Goldman,Rüdiger Hehlmann +31 more
TL;DR: Optimal responders to chronic myeloid leukemia treatment should continue therapy indefinitely, with careful surveillance, or they can be enrolled in controlled studies of treatment discontinuation once a deeper molecular response is achieved.
Journal ArticleDOI
Cancer stem cells: an evolving concept
TL;DR: New insights are obtained into why the CSC concept is not universally applicable, as well as a new basis for understanding the complex evolution, phenotypic heterogeneity and therapeutic challenges of many human cancers.
Journal ArticleDOI
Cancer Stem Cells: Impact, Heterogeneity, and Uncertainty
TL;DR: It remains uncertain whether the stem cell model applies to many, or few, cancers due to questions about the robustness of cancer stem cell markers and the extent to which existing assays underestimate the frequency of tumorigenic cells.
Journal ArticleDOI
Activation of p53 by SIRT1 inhibition enhances elimination of CML leukemia stem cells in combination with imatinib
Ling Li,Lisheng Wang,Liang Li,Zhiqiang Wang,YinWei Ho,Tinisha McDonald,Tessa L. Holyoake,WenYong Chen,Ravi Bhatia +8 more
TL;DR: It is shown that the NAD(+)-dependent deacetylase SIRT1 is overexpressed in human CML LSC and Activation of p53 via Sirt1 inhibition represents a potential approach to target C ML LSC.
Journal ArticleDOI
Chronic myeloid leukemia stem cells are not dependent on Bcr-Abl kinase activity for their survival
Ashley Hamilton,G. Vignir Helgason,Mirle Schemionek,Bin Zhang,Svetlana Myssina,Elaine K. Allan,Franck E. Nicolini,Carsten Müller-Tidow,Ravi Bhatia,Valerie G. Brunton,Steffen Koschmieder,Tessa L. Holyoake +11 more
TL;DR: It is suggested that CML stem cell survival is Bcr-Abl kinase independent and curative approaches in CML must focus on kinase-independent mechanisms of resistance.
References
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Journal ArticleDOI
Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia
Brian J. Druker,François Guilhot,Stephen G. O'Brien,Insa Gathmann,Hagop M. Kantarjian,Norbert Gattermann,Michael W. Deininger,Richard T. Silver,John M. Goldman,Richard Stone,Francisco Cervantes,Andreas Hochhaus,Bayard L. Powell,Janice Gabrilove,Philippe Rousselot,Josy Reiffers,Jan J. Cornelissen,Timothy P. Hughes,Hermine Agis,Thea Kolsen Fischer,Gregor Verhoef,John D. Shepherd,Giuseppe Saglio,Alois Gratwohl,Johan Lanng Nielsen,Jerald P. Radich,Bengt Simonsson,Kerry Taylor,Michele Baccarani,Charlene So,Laurie Letvak,Richard A. Larson +31 more
TL;DR: After 5 years of follow-up, continuous treatment of chronic-phase CML with imatinib as initial therapy was found to induce durable responses in a high proportion of patients.
Journal ArticleDOI
Chronic myeloid leukemia.
TL;DR: This work has demonstrated that CML can be curable through immune-mediated elimination of leukemia cells by allogeneic T lymphocytes, and specific inhibition of signal transduction by the tyrosine kinase Bcr-Abl has been found to be active in managing the disease.
Journal ArticleDOI
Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial
Francois-Xavier Mahon,Delphine Rea,Joelle Guilhot,François Guilhot,Françoise Huguet,Franck E. Nicolini,Laurence Legros,Aude Charbonnier,Agnès Guerci,Bruno Varet,Gabriel Etienne,Josy Reiffers,Philippe Rousselot +12 more
TL;DR: Imatinib discontinuation in this setting yields promising results for molecular relapse-free survival, raising the possibility that, at least in some patients, CML might be cured with tyrosine kinase inhibitors.
Journal ArticleDOI
Frequency of Major Molecular Responses to Imatinib or Interferon Alfa plus Cytarabine in Newly Diagnosed Chronic Myeloid Leukemia
Timothy P. Hughes,Jaspal Kaeda,Susan Branford,Zbigniew Rudzki,Andreas Hochhaus,Martee L. Hensley,Insa Gathmann,Ann E. Bolton,Iris C. van Hoomissen,John M. Goldman,Jerald P. Radich +10 more
TL;DR: The proportion of patients with CML who had a reduction in BCR-ABL transcript levels of at least 3 log by 12 months of therapy was far greater with imatinib treatment than with treatment with interferon plus cytarabine.
Journal ArticleDOI
Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to STI571 in vitro
Susan M. Graham,Heather G. Jørgensen,Elaine K. Allan,Charlie Pearson,Michael J. Alcorn,Linda Richmond,Tessa L. Holyoake +6 more
TL;DR: In vitro insensitivity to STI571, in combination with its demonstrated antiproliferative activity, could translate into disease relapse after prolonged therapy despite dramatic short-term responses in vivo.
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