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Molecular pathogenesis of chronic myeloid leukemia: implications for new therapeutic strategies.

Abstract

With an annual incidence of about ten in 1,000,000 people, chronic myeloid leukemia (CML) accounts for most cases of myeloproliferative disease and for 20% of all leukemias. While novel therapies such as treatment with interferon-alpha or bone marrow transplantation have successively improved the outcome of CML treatment, hope for future progress in the therapy of CML lies in an almost unique feature of this hematological malignancy. In contrast to many other forms or subforms of leukemias which display a great diversity in chromosomal alterations, most cases (>95%) of CML seem to be caused by an almost invariably found cytogenetic aberration, the so-called Philadelphia chromosome (Ph), resulting in the bcr-abl fusion gene. Its gene product, p210bcr-abl (Bcr-Abl), is believed to be essential for hematopoietic cell transformation and seems to exert its effects by interfering with cellular signal transduction pathways, normally involved in the control of cell death and proliferation. Several partially interacting pathways have been shown to be induced by Bcr-Abl. The role of most of them is still unclear and, as understanding their biological functions should lead to novel therapeutic strategies on a molecular basis, much effort is spent on identifying their precise roles in CML. This review focuses on our current understanding of Bcr-Abl-induced signal transduction and outlines its importance for the biological effects of Bcr-Abl.

Authors+Show Affiliations

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Medizinische Klinik III, Klinikum Grosshadern, University of Munich, and Forschungszentrum für Umwelt und Gesundheit (GSF), München, Germany.

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Source

Annals of hematology 78:2 1999 Feb pg 49-64

MeSH

Adaptor Proteins, Signal Transducing
Animals
Apoptosis
Blast Crisis
Calcium-Calmodulin-Dependent Protein Kinases
Cell Adhesion
Cell Division
Cell Transformation, Neoplastic
Cytokines
Fibroblasts
Fusion Proteins, bcr-abl
Gene Expression Regulation, Leukemic
Genes, abl
Growth Substances
Guanine Nucleotides
Hematopoietic Stem Cells
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Mice
Mice, SCID
Mice, Transgenic
Models, Biological
Nuclear Proteins
Philadelphia Chromosome
Phosphatidylinositol 3-Kinases
Phosphoproteins
Proteins
Rats
Receptors, Cytokine
Receptors, Growth Factor
Retinoblastoma-Like Protein p130
Signal Transduction
Structure-Activity Relationship
Transcription Factors
ras Proteins
src-Family Kinases

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

10089019

Citation

Warmuth, M, et al. "Molecular Pathogenesis of Chronic Myeloid Leukemia: Implications for New Therapeutic Strategies." Annals of Hematology, vol. 78, no. 2, 1999, pp. 49-64.
Warmuth M, Danhauser-Riedl S, Hallek M. Molecular pathogenesis of chronic myeloid leukemia: implications for new therapeutic strategies. Ann Hematol. 1999;78(2):49-64.
Warmuth, M., Danhauser-Riedl, S., & Hallek, M. (1999). Molecular pathogenesis of chronic myeloid leukemia: implications for new therapeutic strategies. Annals of Hematology, 78(2), pp. 49-64.
Warmuth M, Danhauser-Riedl S, Hallek M. Molecular Pathogenesis of Chronic Myeloid Leukemia: Implications for New Therapeutic Strategies. Ann Hematol. 1999;78(2):49-64. PubMed PMID: 10089019.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular pathogenesis of chronic myeloid leukemia: implications for new therapeutic strategies. AU - Warmuth,M, AU - Danhauser-Riedl,S, AU - Hallek,M, PY - 1999/3/24/pubmed PY - 1999/3/24/medline PY - 1999/3/24/entrez SP - 49 EP - 64 JF - Annals of hematology JO - Ann. Hematol. VL - 78 IS - 2 N2 - With an annual incidence of about ten in 1,000,000 people, chronic myeloid leukemia (CML) accounts for most cases of myeloproliferative disease and for 20% of all leukemias. While novel therapies such as treatment with interferon-alpha or bone marrow transplantation have successively improved the outcome of CML treatment, hope for future progress in the therapy of CML lies in an almost unique feature of this hematological malignancy. In contrast to many other forms or subforms of leukemias which display a great diversity in chromosomal alterations, most cases (>95%) of CML seem to be caused by an almost invariably found cytogenetic aberration, the so-called Philadelphia chromosome (Ph), resulting in the bcr-abl fusion gene. Its gene product, p210bcr-abl (Bcr-Abl), is believed to be essential for hematopoietic cell transformation and seems to exert its effects by interfering with cellular signal transduction pathways, normally involved in the control of cell death and proliferation. Several partially interacting pathways have been shown to be induced by Bcr-Abl. The role of most of them is still unclear and, as understanding their biological functions should lead to novel therapeutic strategies on a molecular basis, much effort is spent on identifying their precise roles in CML. This review focuses on our current understanding of Bcr-Abl-induced signal transduction and outlines its importance for the biological effects of Bcr-Abl. SN - 0939-5555 UR - https://www.unboundmedicine.com/medline/citation/10089019/Molecular_pathogenesis_of_chronic_myeloid_leukemia:_implications_for_new_therapeutic_strategies_ L2 - http://www.diseaseinfosearch.org/result/1622 DB - PRIME DP - Unbound Medicine ER -