Influence of BCR/ABL fusion proteins on the course of Ph leukemias.

• Authors: Gennady D Telegeev , Anna N Dubrovska , Mykhaylo V Dybkov , Stanislav S Maliuta
• Languages of publication: EN

Abstracts

EN

The hallmark of chronic myeloid leukemia (CML) and a subset of acute lymphoblastic leukemia (ALL) is the presence of the Philadelphia chromosome as a result of the t(9;22) translocation. This gene rearrangement results in the production of a novel oncoprotein, BCR/ABL, a constitutively active tyrosine kinase. There is compelling evidence that the malignant transformation by BCR/ABL is critically dependent on its Abl tyrosine kinase activity. Also the bcr part of the hybrid gene takes part in realization of the malignant phenotype. We supposed that additional mutations accumulate in this region of the BCR/ABL oncogene during the development of the malignant blast crisis in CML patients. In ALL patients having p210 fusion protein the mutations were supposed to be preexisting. Sequencing of PCR product of the BCR/ABL gene (Dbl, PH region) showed that along with single-nucleotide substitutions other mutations, mostly deletions, had occurred. In an ALL patient a deletion of the 5th exon was detected. The size of the deletions varied from 36 to 220 amino acids. For one case of blast crisis of CML changes in the character of actin organization were observed. Taking into account the functional role of these domains in the cell an etiological role of such mutations on the disease phenotype and leukemia progression is plausible.

Keywords

EN

Philadelphia chromosome; actin cytoskeleton; leukemia; BCR/ABL gene

• Journal: Acta Biochimica Polonica
• Year: 2004
• Volume: 51
• Issue: 3
• Pages: 845-849

Dates

published

2004

received

2002-10-25

revised

2003-07-30

accepted

2004-02-26

Contributors

author

Gennady D Telegeev

• Department of Molecular Genetics, Institute of Molecular Biology and Genetics of the NAS of Ukraine, Kyiv, Ukraine

author

Anna N Dubrovska

• Department of Molecular Genetics, Institute of Molecular Biology and Genetics of the NAS of Ukraine, Kyiv, Ukraine

author

Mykhaylo V Dybkov

• Department of Molecular Genetics, Institute of Molecular Biology and Genetics of the NAS of Ukraine, Kyiv, Ukraine

author

Stanislav S Maliuta

• Department of Molecular Genetics, Institute of Molecular Biology and Genetics of the NAS of Ukraine, Kyiv, Ukraine

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