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Molecular biology of chronic myeloid leukemia.
- Source :
-
International journal of hematology [Int J Hematol] 2001 Apr; Vol. 73 (3), pp. 308-22. - Publication Year :
- 2001
-
Abstract
- Multistep carcinogenesis is exemplified by chronic myeloid leukemia with clinical manifestation consisting of a chronic phase and blast crisis. Pathological generation of BCR-ABL (breakpoint cluster region-Abelson) results in growth promotion, differentiation, resistance to apoptosis, and defect in DNA repair in targeted blood cells. Domains in BCR and ABL sequences work in concert to elicit a variety of leukemogenic signals including Ras, STAT5 (signal transducer and activator of transcription-5), Myc, cyclin D1, P13 (phosphatidylinositol 3-kinase), RIN1 (Ras interaction/interference), and activation of actin cytoskeleton. However, the mechanism of differentiation of transformed cells is poorly understood. A mutator phenotype of BCR-ABL could explain the transformation to blast crisis. The aim of this review is to integrate molecular and biological information on BCR, ABL, and BCR-ABL and to focus on how signaling from those molecules mirrors the biological phenotypes of chronic myeloid leukemia.
- Subjects :
- Animals
Blast Crisis genetics
Cell Differentiation
Cell Transformation, Neoplastic genetics
Disease Progression
Fusion Proteins, bcr-abl chemistry
Fusion Proteins, bcr-abl physiology
Gene Expression Regulation, Leukemic
Genes, abl
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive enzymology
Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology
Leukemia, Myeloid, Accelerated Phase genetics
Leukemia, Myeloid, Chronic-Phase genetics
Mice
Mice, Knockout
Models, Biological
Neoplasm Proteins physiology
Neoplastic Stem Cells enzymology
Neoplastic Stem Cells pathology
Oncogene Proteins chemistry
Oncogene Proteins genetics
Oncogene Proteins physiology
Phenotype
Philadelphia Chromosome
Phosphorylation
Protein Processing, Post-Translational
Protein Structure, Tertiary
Proto-Oncogene Proteins c-abl chemistry
Proto-Oncogene Proteins c-abl genetics
Proto-Oncogene Proteins c-abl physiology
Proto-Oncogene Proteins c-bcr
Rats
Signal Transduction
Structure-Activity Relationship
Fusion Proteins, bcr-abl genetics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics
Protein-Tyrosine Kinases
Proto-Oncogene Proteins
Subjects
Details
- Language :
- English
- ISSN :
- 0925-5710
- Volume :
- 73
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- International journal of hematology
- Publication Type :
- Academic Journal
- Accession number :
- 11345196
- Full Text :
- https://doi.org/10.1007/BF02981955