Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ablation of c-Myb function might be an effective approach for the therapy of chronic myelogenous leukemia or other c-myb-dependent malignancies. To this end, we have previously used an intracellular anti-c-Myb single-chain antibody (sFv) to achieve the functional knockout of the c-Myb oncoprotein. In this study, we have employed a tetracycline-inducible system to control the expression of the sFv. A nuclear-localizing form of an anti-c-Myb sFv was cloned into a tet-regulated plasmid vector. Using a transient expression system in COS-1 cells, we observed that doxycycline (Dox) induced expression of the sFv in a dose-dependent manner, and that the sFv was localized mainly in the nucleus. The Dox-induced anti-c-Myb sFv also inhibited the transactivating activity of c-Myb in a dose-dependent manner. We subsequently confirmed the Dox-induced expression of the sFv in the leukemia cell line K562. Proliferation of the target leukemia cells was also inhibited. These results suggest that the anti-c-Myb sFv may represent a viable method for gene therapy of c-myb-dependent hematopoietic malignancies.
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PMID:Tetracycline-induced expression of an anti-c-Myb single-chain antibody and its inhibitory effect on proliferation of the human leukemia cell line K562. 1067 68

The Bcr/Abl oncogene is responsible for the development of Ph-chromosome positive acute lymphoblastic leukemia and chronic myelogenous leukemia in humans. Previous studies demonstrated that Bcr/Abl expression is associated with elevated levels of activated Rap1, a small GTPase. Levels of activated Rap1 are determined by a balance between GTPase activating and G-nucleotide exchange factor activity. We show that Bcr/Abl forms a protein-protein complex with Spa-1, a GTPase activating protein for Rap1, both in COS-1 cells as well as in primary lymphoblastic leukemia cells from a transgenic P190 BCR/ABL mouse model. The interaction between Spa-1 and P190 did not affect the tyrosine kinase activity of P190, nor did Spa-1 become phosphorylated on tyrosine as a result of the interaction. P190 and Spa-1 co-localized to peripheral actin structures in primary lymphoblasts and expression of Spa-1 in the leukemic lymphoblasts decreased the migration of these cells. The binding of Bcr/Abl to Spa-1 may cause aberrant subcellular location of Spa-1 and affect migration of these cells.
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PMID:Bcr/Abl P190 interaction with Spa-1, a GTPase activating protein for the small GTPase Rap1. 1881 51


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