IntroductionChronic myeloid leukemia (CML) is a clonal disorder of pluripotent hematopoietic cells that is characterized by the presence of the Philadelphia chromosome (Ph ϩ ), the result of a reciprocal translocation between chromosomes 9 and 22. The translocation encodes a chimeric protein, BCR-ABL, which is a constitutively activated protein tyrosine kinase (PTK) 1 and which has an essential role in the molecular pathology of CML. CML is a progressive disease with an initial chronic phase in which there is a marked expansion in the late myeloid cell population (reviewed by Clarkson and Strife 2 ). CML progenitor cells possess only a subtle defect in maturation, while retaining their requirements for bone marrow stromal cells or cytokines to survive and proliferate. 3 This chronic phase, which is of variable duration, is usually followed by an accelerated phase leading to blast crisis. The blast crisis is the most severe manifestation of the disease in which differentiation is apparently blocked. Imatinib (Gleevec or STI571), an Abl tyrosine kinase inhibitor, is the first line and gold standard for treating CML. Nonetheless, there is clear evidence of resistance to this drug. The development of other approaches to treat the disease with smallmolecule inhibitors to new targets has been, and will be, a focus for future research into treatment of imatinib-resistant patients and those in accelerated phase or blast crisis. [4][5][6][7] Thus, understanding the process of leukemogenesis driven by this oncogene is still an important research objective.Most cell-line models expressing BCR-ABL PTK are already differentiation blocked, and assume a growth factor-independent phenotype. [8][9][10][11] In this respect they mirror the properties of cells from patients with CML in blast crisis. However, we have established a cell-line model for CML that has properties of chronic-phase progenitor cells that progressively change to those resembling accelerated phase by using an inducible temperaturesensitive BCR-ABL PTK (ts-BCR-ABL FDCP-Mix). 12-14 DNA microarray technology has been used to identify differential expression as a result of the initial activation of BCR-ABL. Activation of BCR-ABL in FDCP-Mix cells has identified transcriptional and secretory events regulated by BCR-ABL. These effects are observed to be due to BCR-ABL in primary CML cells. Materials and methods Cell linesFDCP-Mix cells transfected with the retroviral vector pM5-neo carrying a p210 ts-BCR-ABL cDNA were used as a model system for CML. 12 The L.M. carried out the majority of the practical work, data analysis, and interpretation, and contributed to preparation of the manuscript; S.P. played a major part in experimental design and execution; N.P. and B.P. provided essential biological material and made a major contribution to the interpretation of data; A.P. and A.D.W. provided essential biological reagents and contributed to experimental design and writing of the manuscript; A.E.I. was responsible for the overall conception and design of the project, in...
This study demonstrated that PEI occurs at a higher rate than previously reported; clinicians need to diagnose and treat this SSA-related adverse-event which occurs in 1 in 4 patients with Wd-NETs treated with SSAs. Screening with FE1 in symtomatic patients is recommend.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.