Abstract
Objective: To survey the role of protein tyrosine kinases (PTKs) in the pathogenesis of several hematopoietic malignancies. Methods: By reviewing the published laboratory and clinical studies on PTK-related oncoproteins and their causative role in some leukemias and lymphomas. Results: Protein tyrosine kinases are key participants in signal transduction pathways that regulate cellular growth, activation and differentiations. Aberrant PTK activity resulting from gene mutation (often accompanying chromosome translocation) plays an etiologic role in several clonal hematopoietic malignancies. For example, the PTK product of the BCR-ABL fusion gene resulting from the t (9; 22) translocation exhibits several fold higher tyrosine kinase activity than the product of the ABL gene. Evidence suggests that the BCR-ABL oncoprotein alone is sufficient to case chronic myelogenous leukemia (CML) and other Ph positive acute leukemia. PTK over-activity resulting from chromosomal translocations creating TEL-ABL, TEL-JAK2 and TEL-PDGFRβ fusion proteins plays an important role in the pathogenesis of other types of leukemia. Another example occurs in anaplastic large cell lymphoma (ALCL). Experimental and clinical evidences indicate that translocations involving ALK gene on chromosome 2p23, most commonly resulting in an NPM-ALK fusion oncogene, result in constitutive activation of ALK and cause ALCL. This group of lymphomas is now named ALK positive lymphoma or ALKoma. Conclusion: Genetic lesions creating aberrant fusion proteins that result in excessive PTK activity are increasingly being recognized as central to the pathogenesis of hemotopoietic malignancies. These chimeric PTK molecules represent attractive disease-specific targets against which new classes therapeutic agents are being developed.
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Foundation item: This work was partially supported by a grant from World Health Organization Fellowship (XS) (WPRO AWARD No. 0008/99).
Biography: Sun Xue-mei(1964–), female, master of medicine, associate professor, Medical Research Center, Nanjing University, Drum Tower Hospital, majors in hematology.
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Sun, Xm., Lieschke, G.J. Abnormal protein tyrosine kinases associated with human haematological malignancies. Chin. J. Cancer Res. 14, 79–83 (2002). https://doi.org/10.1007/s11670-002-0018-3
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DOI: https://doi.org/10.1007/s11670-002-0018-3
Key words
- Protein tyrosine kinase (PTK)
- Hematopoietic malignancy
- BCR-ABL
- Chronic myelogenous leukemia (CML)
- Anaplastic large cell lymphoma (ALCL)
- STI 571
- Protein tyrosine kinase inhibitor