Related Experiment Videos
Haemopoietic transformation by the TEL/ABL oncogene
J R Hannemann1, D M McManus, J H Kabarowski
1Leukaemia Research Fund Centre at the Institute of Cancer Research, Chester Beatty Laboratories, London.
British Journal of Haematology
|August 8, 1998
Summary
Novel TEL/ABL fusion proteins activate ABL kinase in hematopoietic diseases. The TEL/ABL type A fusion, lacking a Grb2 binding site, promotes factor independence in precursor cells.
Area of Science:
- Oncology
- Molecular Biology
- Hematology
Background:
- Activated ABL kinase is implicated in hematopoietic malignancies.
- Fusion proteins, such as TEL/ABL, arise from chromosomal translocations.
- Understanding the mechanisms of ABL kinase activation is crucial for targeted therapies.
Purpose of the Study:
- To analyze the functional properties of the TEL/ABL fusion protein (type A) found in acute lymphoblastic leukemia.
- To investigate the role of specific TEL domains in ABL kinase activation.
- To compare the type A TEL/ABL fusion with other known variants.
Main Methods:
- Cloning and expression of the type A TEL/ABL fusion cDNA.
- Assessing tyrosine kinase activity and in vivo protein phosphorylation.
- Evaluating the effect of TEL/ABL expression on hematopoietic precursor cell proliferation and survival.
- Analyzing protein self-association and mRNA expression levels.
Main Results:
- The type A TEL/ABL fusion encodes a 155 kD protein with elevated tyrosine kinase activity.
- Expression of type A TEL/ABL confers factor independence to murine hematopoietic precursor cells.
- These cells maintain high myc mRNA levels and exhibit factor independence.
- Type A TEL/ABL proteins demonstrate self-association in hematopoietic cells.
Conclusions:
- The protein interaction domain of TEL, similar to BCR, is critical for ABL kinase activation.
- The Grb2 binding site in TEL is not essential for the activation of ABL kinase in hematopoietic diseases.
- Oligomerization domains in fusion proteins play a key role in aberrant kinase activity.