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Lineage-specific requirement of c-abl function in normal hematopoiesis
D Caracciolo1, M Valtieri, D Venturelli
1Istituto di Medicina ed Oncologia Sperimentale, Sezione di Ematologia, Torino, Italy.
Science (New York, N.Y.)
|September 8, 1989
Summary
The c-abl proto-oncogene is crucial for normal myeloid cell development. Inhibiting c-abl with antisense oligodeoxynucleotides specifically blocked myeloid colony formation, suggesting its role in myelopoiesis.
Area of Science:
- Hematology
- Molecular Biology
- Oncology
Background:
- Structural abnormalities of the c-abl proto-oncogene are prevalent in chronic myelogenous leukemia (CML).
- The c-abl proto-oncogene's role in normal hematopoiesis is not fully understood.
- CML is characterized by the selective expansion of leukocytes.
Purpose of the Study:
- To investigate the role of the c-abl proto-oncogene in normal human hematopoiesis.
- To determine the specific effects of c-abl modulation on myeloid and erythroid progenitor cells.
Main Methods:
- Normal human hematopoietic progenitor cells were treated with c-abl sense or antisense oligodeoxynucleotides.
- The impact on myeloid and erythroid colony formation was assessed.
- Control experiments included bcr sense and antisense oligodeoxynucleotides.
Main Results:
- c-abl antisense oligodeoxynucleotides significantly inhibited myeloid colony formation.
- Erythroid colony formation was not affected by c-abl antisense oligodeoxynucleotides.
- c-abl sense, bcr sense, and bcr antisense oligodeoxynucleotides showed no inhibitory effects.
Conclusions:
- The c-abl proto-oncogene is critical for normal myelopoiesis.
- These findings may explain the selective proliferation of leukocytes in CML.
- Targeting c-abl could be a potential therapeutic strategy for CML.