Expression of p210 BCR ABL increases hematopoietic progenitor cell radiosensitivity

Maria A. Santucci, Pervin Anklesaria, Pierre Laneuville, Indra J. Das, Mary Ann Sakakeeny, T. J. Fitzgerald, Joel S. Greenberger

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Purpose: The cytogenetic finding of the Ph1+ chromosome and its molecular biologic marker bcr/abl gene rearrangement in cells from patients with chronic myeloid leukemia are associated with a proliferative advantage of the Ph1+ clone in vivo. Although the transition to the acute terminal phase or blastic crisis is often associated with additional cytogenetic abnormalities, the molecular events which correlate the initial cytogenetic lesion with the terminal phase are poorly understood. Defective cellular DNA repair capacity is often associated with chromosomal instability, increased mutation frequency, and biologic alterations. Methods and Materials: We, therefore, tested whether the protein product of the bcr/abl translocation (p210) could alter DNA repair after gamma-irradiation of murine cell lines expressing the bcr/abl cDNA. Results: The 32D cl 3 parent, 32D cl 3 pYN (containing the control vector plasmid) and each of two sources of 32D cl 3 cells expressing p210 bcr/abl cDNA (32D-PC1 cell line and 32D-LG7 subclone) showed a D0 of 1.62, 1.57, 1.16, and 1.27 Gy, respectively. Thus, expression of the p210 bcr/abl product induced a significant (p <0.05) increase in radiosensitivity at the clinically relevant radiation therapy dose-rate (1.16 Gy/min). The increased radiosensitivity of p210 bcr/abl expressing cells persisted if cells were held before plating in a density-inhibited state for 8 hr after gamma-irradiation, indicating little effect on the repair of potentially lethal gamma-irradiation damage. The IL-3 dependent parent 32D cl 3 cells demonstrated programmed cell death in the absence of growth factor or following gamma-irradiation to 200 cGy. Expression of bcr/abl cDNA in the 32D-PC1 and 32D-LG7 sub clones abrogated IL-3 requirement of these cell lines and inhibited gamma-irradiation induced programmed cell death. Conclusion: These data suggest a role for bcr/abl p210 in amplifying gamma-irradiation DNA damage or broadly inhibiting DNA repair, conditions that may stimulate further cytogenetic alterations in hematopoietic cells.

Original languageEnglish (US)
Pages (from-to)831-836
Number of pages6
JournalInternational Journal of Radiation Oncology Biology Physics
Volume26
Issue number5
DOIs
StatePublished - Aug 1 1993
Externally publishedYes

Fingerprint

Radiation Tolerance
radiation tolerance
Hematopoietic Stem Cells
irradiation
deoxyribonucleic acid
cells
cultured cells
Cytogenetics
DNA Repair
Complementary DNA
Interleukin-3
apoptosis
Cell Line
Cell Death
Clone Cells
abl Genes
directional control
damage
Philadelphia Chromosome
Chromosomal Instability

Keywords

  • bcr/abl
  • Chronic myelogenous leukemia
  • Radiosensitivity

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

Santucci, M. A., Anklesaria, P., Laneuville, P., Das, I. J., Sakakeeny, M. A., Fitzgerald, T. J., & Greenberger, J. S. (1993). Expression of p210 BCR ABL increases hematopoietic progenitor cell radiosensitivity. International Journal of Radiation Oncology Biology Physics, 26(5), 831-836. https://doi.org/10.1016/0360-3016(93)90498-K

Expression of p210 BCR ABL increases hematopoietic progenitor cell radiosensitivity. / Santucci, Maria A.; Anklesaria, Pervin; Laneuville, Pierre; Das, Indra J.; Sakakeeny, Mary Ann; Fitzgerald, T. J.; Greenberger, Joel S.

In: International Journal of Radiation Oncology Biology Physics, Vol. 26, No. 5, 01.08.1993, p. 831-836.

Research output: Contribution to journalArticle

Santucci, MA, Anklesaria, P, Laneuville, P, Das, IJ, Sakakeeny, MA, Fitzgerald, TJ & Greenberger, JS 1993, 'Expression of p210 BCR ABL increases hematopoietic progenitor cell radiosensitivity', International Journal of Radiation Oncology Biology Physics, vol. 26, no. 5, pp. 831-836. https://doi.org/10.1016/0360-3016(93)90498-K
Santucci, Maria A. ; Anklesaria, Pervin ; Laneuville, Pierre ; Das, Indra J. ; Sakakeeny, Mary Ann ; Fitzgerald, T. J. ; Greenberger, Joel S. / Expression of p210 BCR ABL increases hematopoietic progenitor cell radiosensitivity. In: International Journal of Radiation Oncology Biology Physics. 1993 ; Vol. 26, No. 5. pp. 831-836.
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