In vitro transformation of immature hematopoietic cells by the P210 BCR/ABL oncogene product of the Philadelphia chromosome
The Philadelphia chromosome is the cytogenetic hallmark of human chronic myelogenous leukemia. RNA splicing joins sequences from a gene on chromosome 22 (BCR) across the translocation breakpoint to a portion of the ABL oncogene from chromosome 9, resulting in a chimeric protein (P210) that is an active tyrosine kinase. Although strongly correlated with this specific human neoplasm, and implicated as an oncogene by analogy to the gene product of the Abelson murine leukemia virus, the P210 gene had not been tested directly for oncogenic potential in hematopoietic cells. The authors have used a retroviral gene-transfer system to express P210 in mouse bone marrow cells. When infected bone marrow is plated under conditions for long-term culture of cells of the B-lymphoid lineage, cells expressing high amounts of P210 tyrosine kinase dominate the culture and rapidly lead to clonal outgrowths of immature lymphoid cells. Expression of P210 is growth-stimulatory but not sufficient for full oncogenic behavior. Some clonal lines progress toward a fully malignant phenotype as judged by increased cloning efficiency in agar suspension and frequency and rapidity of tumor induction in syngeneic mice. Such in vitro systems should be useful in evaluating the sequential and perhaps synergistic involvement of the P210 gene and other oncogenes as models for the progressive changes observed in human chronic myelogenous leukemia.
- Research Organization:
- Univ. of California, Los Angeles (USA)
- OSTI ID:
- 7141786
- Journal Information:
- Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 84:18
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
BONE MARROW CELLS
ENZYME ACTIVITY
ONCOGENIC TRANSFORMATIONS
ONCOGENES
AUTORADIOGRAPHY
PHOSPHOTRANSFERASES
ATP
ELECTROPHORESIS
GENE RECOMBINATION
IN VITRO
LEUKEMIA
MESSENGER-RNA
METHIONINE
PATIENTS
PHILADELPHIA CHROMOSOME
PHOSPHORUS 32
SULFUR 35
TRANSCRIPTION
TYROSINE
AMINO ACIDS
ANIMAL CELLS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CARBOXYLIC ACIDS
CELL TRANSFORMATIONS
CHROMOSOMES
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DISEASES
DRUGS
ENZYMES
EVEN-ODD NUCLEI
GENES
HEMIC DISEASES
HYDROXY ACIDS
ISOTOPES
LIGHT NUCLEI
LIPOTROPIC FACTORS
NEOPLASMS
NUCLEI
NUCLEIC ACIDS
NUCLEOTIDES
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PHOSPHORUS ISOTOPES
PHOSPHORUS-GROUP TRANSFERASES
RADIOISOTOPES
RNA
SOMATIC CELLS
SULFUR ISOTOPES
TRANSFERASES
550601* - Medicine- Unsealed Radionuclides in Diagnostics
550201 - Biochemistry- Tracer Techniques