Rational Approaches to the Design of Therapeutics Targeting Molecular Markers: The Case of Chronic Myelogenous Leukemia

@article{Saglio2004RationalAT,
  title={Rational Approaches to the Design of Therapeutics Targeting Molecular Markers: The Case of Chronic Myelogenous Leukemia},
  author={Giuseppe Saglio and Alessandro Morotti and Giovanna Mattioli and Emanuela Messa and Emilia Giugliano and Gisella Volpe and Giovanna Rege‐Cambrin and Daniela Cilloni},
  journal={Annals of the New York Academy of Sciences},
  year={2004},
  volume={1028}
}
Abstract: Progress in understanding the molecular basis of signal transmission and transduction has contributed substantially to clarifying the mechanisms of leukemogenesis and of leukemia progression and has led to the identification of a number of specific molecular targets for treatment. Chronic myeloid leukemia (CML) has provided one of the best models, as the identification of a leukemia‐specific hybrid tyrosine kinase (BCR‐ABL, p210, p190) has led to the identification and the successful… 
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26 Citations

Strategies For Targeting Chronic Myeloid Leukaemia Stem Cells
TLDR
New insights into the mechanisms of resistance to TKIs are summarized and it remains clear that tyrosine kinase inhibitors are unable to target the most immature cellular component of CML, the CML stem cell.
Protein Kinase CK2: A Targetable BCR-ABL Partner in Philadelphia Positive Leukemias
TLDR
The role of BCR-ABL/protein kinase CK2 interaction in BCR -ABL leukemias is reviewed, with potentially relevant implications for therapy.
The BCR-ABL/NF-κB signal transduction network: a long lasting relationship in Philadelphia positive Leukemias
TLDR
The role of NF-κB in BCR-ABL-mediated leukemogenesis is summarized and new insights are provided on the long lasting BCR -ABL/NF-κBs connection.
BLCTT_A_228815 45..52
TLDR
A review summarizes new insights into the mechanisms of resistance to TKIs and shows that tyrosine kinase inhibitors are unable to target the most immature cellular component of CML, the CML stem cell.
Non genomic loss of function of tumor suppressors in CML: BCR-ABL promotes IκBα mediated p53 nuclear exclusion
TLDR
It is shown that BCR-ABL promotes the accumulation of the NFKBIA gene product, IκBα, in the cytosol through physical interaction and stabilization of the protein, and a novel B CR-AB l/IκB α/p53 network functionally inactivates a key tumor suppressor.
A Case Report of Personalized Chemotherapy for Metastatic Cardiac Sarcoma
TLDR
A personalized chemotherapy to treat a patient suffering from cardiac sarcoma with multiple metastases is reported, successfully select FDA approved drugs to treat the patient and achieve a partial response for the patient.
Cytogenetic investigation in chronic myeloid leukemia: study from an Indian population.
TLDR
Availability of more advanced molecular techniques can be used as a supportive tool in CML diagnosis even though it cannot fully replace cytogenetics, which remains the backbone for laboratory investigation of the disease.
Potential use of nucleic acid-based agents in the sensitization of nasopharyngeal carcinoma to radiotherapy.
BCR-ABL inactivates cytosolic PTEN through Casein Kinase II mediated tail phosphorylation
TLDR
It is shown that nuclear exclusion of PTEN is associated with PTEN inactivation in the cytoplasm of CML cells, and a novel BCR-ABL/CKII/PTEN pathway is proposed as a potential target to achieve synthetic lethality with tyrosine kinase inhibitors.
Nuclear-cytoplasmic Shuttling in Chronic Myeloid Leukemia: Implications in Leukemia Maintenance and Therapy
TLDR
The role of various shuttling components in Chronic Myeloid Leukemia is recapitulate and insights are provided on the potential role ofshuttling proteins as therapeutic targets.
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