Chronic myeloid leukaemia as a model of disease evolution in human cancer

@article{Melo2007ChronicML,
  title={Chronic myeloid leukaemia as a model of disease evolution in human cancer},
  author={Junia V. Melo and David J. Barnes},
  journal={Nature Reviews Cancer},
  year={2007},
  volume={7},
  pages={441-453}
}
Chronic myeloid leukaemia (CML) can be considered as a paradigm for neoplasias that evolve through a multi-step process. CML is also one of the best examples of a disease that can be targeted by molecular therapy; however, the success of new 'designer drugs' is largely restricted to the chronic phase of the disease. If not cured at this stage, CML invariably progresses and transforms into an acute-type leukaemia undergoing a 'blast crisis'. The causes of this transformation are still poorly… Expand
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References

SHOWING 1-10 OF 186 REFERENCES
Investigation on the role of the ATM gene in chronic myeloid leukaemia
TLDR
A mutational analysis for ATM using genomic DNA from 14 CML cell lines and 59 CML patients in BC found a new polymorphism C4138T was discovered which results in a non-conservative amino acid substitution (H1380Y), which lies in the Atm recognition motif for the Abl protein. Expand
Dynamics of chronic myeloid leukaemia
TLDR
A four-compartment model, based on the known biology of haematopoietic differentiation, can explain the kinetics of the molecular response to imatinib in a 169-patient data set and provides the first quantitative insights into the in vivoKinetics of a human cancer. Expand
The biology of CML blast crisis.
TLDR
Validation of the critical role of certain secondary changes (ie, loss of p53 or C/EBPalpha function) in murine models of CML blast crisis and in in vitro assays of BCR/ABL transformation of human hematopoietic progenitors might lead to the development of novel therapies based on targeting BCR /ABL and inhibiting or restoring the gene activity gained or lost during disease progression. Expand
Cooperation of BCR-ABL and AML1/MDS1/EVI1 in blocking myeloid differentiation and rapid induction of an acute myelogenous leukemia
TLDR
It is demonstrated that AME alone does not block myeloid differentiation in vivo during the 4-month pre-leukemia stage, yet co-expression of BCR-ABL and AME in mice can block myELoid differentiation and rapidly induce an AML. Expand
Blasts from the past: new lessons in stem cell biology from chronic myelogenous leukemia.
TLDR
A recent report by sheds new light on leukemia stem cells by identifying the cells with in vitro self-renewing properties in various phases of chronic myelogenous leukemia, and linking the self-Renewal properties of this population to activation of beta-catenin, a major effector of the canonical Wnt signaling pathway. Expand
Mutations of the myeloid transcription factor CEBPA are not associated with the blast crisis of chronic myeloid leukaemia
TLDR
No CEBPA mutation in 95 CML‐BC patients was found, suggesting a limited role, if any, ofCEBPA mutations in this disorder, suggesting the inevitable evolution of chronic myeloid leukaemia in chronic phase (CP) to a fatal blast crisis (BC). Expand
FTY720, a New and Alternative Strategy for Treating Blast Crisis CML and Ph 1 ALL Patients.
TLDR
The results strongly support the use of this PP2A activator FTY720 as a novel therapeutic approach for CML-BC and Ph1 ALL and reinforce the importance of the PP 2A tumor suppressor in the biology of Ph1 leukemias. Expand
Characterization of stage progression in chronic myeloid leukemia by DNA microarray with purified hematopoietic stem cells
TLDR
Compared with DNA microarray the expression profiles of 3456 genes in the purified HSC-like fractions that had been isolated from 13 CML patients and healthy volunteers suggest that microarray analysis with background-matched samples is an efficient approach to identify molecular events underlying the stage progression in CML. Expand
Enhanced expression and activity of DNA polymerase beta in chronic myelogenous leukemia.
TLDR
The results suggest that the excess of pol beta in CML could contribute to the genetic instability observed during the evolution of the disease from the chronic phase to blast crisis. Expand
Genomic p16 abnormalities in the progression of chronic myeloid leukemia into blast crisis: a sequential study in 42 patients.
TLDR
P16 gene deletions are detected in a substantial proportion of lymphoid BC of CML by quantitative real-time PCR analysis, but this is not associated with any clinico-hematological feature other than lymphoid phenotype and does not influence the patients' outcome. Expand
...
1
2
3
4
5
...