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Transduction-Transplantation Mouse Model of Myeloproliferative Neoplasm
Published on: December 22, 2016
PML-RARA fusion transcripts in irradiated and normal hematopoietic cells
A S Quina1, P Gameiro, M Sá da Costa
1Institute of Histology and Embryology, Lisbon Medical School, Lisbon, Portugal.
Genes, Chromosomes & Cancer
|September 19, 2000
Summary
Chromosomal translocations like PML-RARA in acute promyelocytic leukemia (APL) are not easily induced by DNA damage, even with gene proximity. These rearrangements occur naturally in normal hematopoietic cells without causing cancer.
Area of Science:
- Genetics
- Molecular Biology
- Cancer Research
Background:
- Reciprocal chromosomal translocations in cancer often arise from gene proximity and chromatin structure.
- The PML-RARA fusion transcript is a hallmark of acute promyelocytic leukemia (APL).
Purpose of the Study:
- To investigate if a clastogenic agent can induce PML-RARA fusion transcripts in cells with pre-existing gene proximity.
- To determine the susceptibility of PML and RARA genes to gamma-irradiation-induced breakage.
Main Methods:
- Irradiation of a lymphoid cell line with close PML and RARA genes using gamma rays.
- Analysis of PML-RARA transcript incidence via sensitive PCR assays.
- Detection of PML-RARA transcripts in normal peripheral blood cells.
Main Results:
- PML-RARA transcripts were rarely detected in irradiated cells, similar to non-irradiated controls.
- Low frequencies of PML-RARA transcripts were found in normal lymphoid and granulocytic cells.
- The PML and RARA genes showed low susceptibility to gamma-irradiation-induced clastogenesis.
Conclusions:
- Gene proximity alone does not guarantee translocation induction by clastogenic agents.
- PML-RARA rearrangements can occur spontaneously in normal hematopoietic cells across lineages.
- These spontaneous rearrangements may not necessarily lead to oncogenic consequences.

