Journal ArticleDOI
Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia.
Reads0
Chats0
TLDR
Although BCR–ABL remains an attractive therapeutic target, it is important to identify other components involved in CML pathogenesis to overcome this resistance.Abstract:
Imatinib, a potent inhibitor of the oncogenic tyrosine kinase BCR-ABL, has shown remarkable clinical activity in patients with chronic myelogenous leukaemia (CML). However, this drug does not completely eradicate BCR-ABL-expressing cells from the body, and resistance to imatinib emerges. Although BCR-ABL remains an attractive therapeutic target, it is important to identify other components involved in CML pathogenesis to overcome this resistance. What have clinical trials of imatinib and studies using mouse models for BCR-ABL leukaemogenesis taught us about the functions of BCR-ABL beyond its kinase activity, and how these functions contribute to CML pathogenesis?read more
Citations
More filters
Journal ArticleDOI
The epigenetic progenitor origin of human cancer
TL;DR: This work suggests that non-neoplastic but epigenetically disrupted stem/progenitor cells might be a crucial target for cancer risk assessment and chemoprevention.
Journal ArticleDOI
Acute lymphoblastic leukaemia
TL;DR: Advances in understanding of the pathobiology of acute lymphoblastic leukaemia, fuelled by emerging molecular technologies, suggest that drugs specifically targeting the genetic defects of leukaemic cells could revolutionise management of this disease.
Journal ArticleDOI
Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by β-phenylethyl isothiocyanate
Dunyaporn Trachootham,Yan Zhou,Hui Zhang,Hui Zhang,Y. Demizu,Zhao Chen,Zhao Chen,Helene Pelicano,Paul J. Chiao,Paul J. Chiao,Geetha Achanta,Ralph B. Arlinghaus,Ralph B. Arlinghaus,Jinsong Liu,Jinsong Liu,Peng Huang,Peng Huang +16 more
TL;DR: It is shown that abnormal increases in ROS can be exploited to selectively kill cancer cells using beta-phenylethyl isothiocyanate (PEITC), which exhibits therapeutic activity and prolongs animal survival in vivo.
Journal ArticleDOI
Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia
Chen Zhao,Alan Chen,Catriona Jamieson,Mark Fereshteh,Annelie Abrahamsson,Jordan M. Blum,Hyog Young Kwon,Jynho Kim,John P. Chute,David A. Rizzieri,Michael John Munchhof,Todd VanArsdale,Philip A. Beachy,Tannishtha Reya +13 more
TL;DR: It is shown that the loss of Smoothened (Smo), an essential component of the Hh pathway, impairs haematopoietic stem cell renewal and decreases induction of chronic myelogenous leukaemia (CML) by the BCR–ABL1 oncoprotein.
Journal ArticleDOI
Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia.
Andreas Hochhaus,Stephen G. O'Brien,François Guilhot,B. J. Druker,Susan Branford,Letizia Foroni,JohnM. Goldman,Martin C. Müller,Jerald P. Radich,Marc Rudoltz,Manisha Mone,Insa Gathmann,Timothy P. Hughes,Richard A. Larson +13 more
TL;DR: During the sixth year of study treatment, there were no reports of disease progression to accelerated phase (AP) or blast crisis (BC), and the toxicity profile was unchanged.
References
More filters
Journal ArticleDOI
The phosphatidylinositol 3-Kinase AKT pathway in human cancer.
Igor Vivanco,Charles L. Sawyers +1 more
TL;DR: Small-molecule therapeutics that block PI3K signalling might deal a severe blow to cancer cells by blocking many aspects of the tumour-cell phenotype.
Journal Article
ras Oncogenes in Human Cancer: A Review
TL;DR: It appeared that ras gene mutations can be found in a variety of tumor types, although the incidence varies greatly and some evidence that environmental agents may be involved in the induction of the mutations.
Journal ArticleDOI
Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells.
Brian J. Druker,Shu Tamura,Elisabeth Buchdunger,Sayuri Ohno,Gerald M. Segal,Shane Fanning,Jürg Zimmermann,Nicholas B. Lydon +7 more
TL;DR: A compound, designed to inhibit the Abl protein tyrosine kinase, was evaluated for its effects on cells containing the Bcr–Abl fusion protein and it was found that this compound may be useful in the treatment of bcr–abl–positive leukemias.
Journal ArticleDOI
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.
Related Papers (5)
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