Expression and regulation of bcl-2 and bcl-xl correlate with p53 status in childhood acute lymphoblastic leukemia

L. Gu, Andrew M Yeager, H. W. Findlev

Research output: Contribution to journalArticle

Abstract

Bcl-2 and its homologue, Bcl-xl, encode proteins that protect neoplastic cells from DNA damage-induced apoptosis. In the present study, we examined the expression of Bd-2 and Bcl-xl in 22 pédiatrie acute lymphoblastic leukemia (ALL) cell lines by Northern blotting, and the regulation of Bcl-2 and Bcl-xl in these ALL lines in response to apoptosis induced by ionizing radiation (IR). Nine of 22 (41%) ALL lines expressed Bcl~2, and all 22 lines were positive for Bcl-xl. As we previously reported (Blood 85:1608,1995), U of 22 lines expressed wild-type (wt) p53, 4 expressed mutant p53, and 7 were p53-. Of the 9 Bcl-2+ ALL lines, 8 were wt~ p53+ and one expressed mutant p53; Bcl-2 was not expressed in any p53- lines. Although levels of Bcl-xl expression were variable among the 22 lines, marked overexpression of Bcl-xl was observed in 5 of 7 p53- lines, Treatment with IR (10 Gy) induced down-regulation of Bcl-2 at 2-5 hours in wt-pS3+ lines, leading to apoptosis, but not in the mutant p53+ line, which was resistant to apoptosis. There were no obvious changes in the expression of Bcl-xl in these lines after IR treatment. However, among the p53- ALL lines, resistance to IR was observed in lines overexpressing Bcl-xl but not in lines lacking Bcl-xl overexpression. These results suggest that expression of Bcl-2 but not Bcl-xl is wt-p53 dependent, and that IRinduced downregulation of Bcl-2 occurs in wt-p53+ lines and is associated with radiosensitivity, Furthermore, overexpression of Bcl-xl occurs only in p53- lines and is associated with resistance to IR-induced apoptosis in these lines, indicating differential expression and regulation of Bcl-2 and Bcl-xl in pédiatrie ALL.

Original languageEnglish (US)
Pages (from-to)1124
Number of pages1
JournalExperimental Hematology
Volume24
Issue number9
StatePublished - 1996
Externally publishedYes

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Ionizing Radiation
Apoptosis
Down-Regulation
Radiation Tolerance
Northern Blotting
DNA Damage
Cell Line
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

Cite this

Expression and regulation of bcl-2 and bcl-xl correlate with p53 status in childhood acute lymphoblastic leukemia. / Gu, L.; Yeager, Andrew M; Findlev, H. W.

In: Experimental Hematology, Vol. 24, No. 9, 1996, p. 1124.

Research output: Contribution to journalArticle

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abstract = "Bcl-2 and its homologue, Bcl-xl, encode proteins that protect neoplastic cells from DNA damage-induced apoptosis. In the present study, we examined the expression of Bd-2 and Bcl-xl in 22 p{\'e}diatrie acute lymphoblastic leukemia (ALL) cell lines by Northern blotting, and the regulation of Bcl-2 and Bcl-xl in these ALL lines in response to apoptosis induced by ionizing radiation (IR). Nine of 22 (41{\%}) ALL lines expressed Bcl~2, and all 22 lines were positive for Bcl-xl. As we previously reported (Blood 85:1608,1995), U of 22 lines expressed wild-type (wt) p53, 4 expressed mutant p53, and 7 were p53-. Of the 9 Bcl-2+ ALL lines, 8 were wt~ p53+ and one expressed mutant p53; Bcl-2 was not expressed in any p53- lines. Although levels of Bcl-xl expression were variable among the 22 lines, marked overexpression of Bcl-xl was observed in 5 of 7 p53- lines, Treatment with IR (10 Gy) induced down-regulation of Bcl-2 at 2-5 hours in wt-pS3+ lines, leading to apoptosis, but not in the mutant p53+ line, which was resistant to apoptosis. There were no obvious changes in the expression of Bcl-xl in these lines after IR treatment. However, among the p53- ALL lines, resistance to IR was observed in lines overexpressing Bcl-xl but not in lines lacking Bcl-xl overexpression. These results suggest that expression of Bcl-2 but not Bcl-xl is wt-p53 dependent, and that IRinduced downregulation of Bcl-2 occurs in wt-p53+ lines and is associated with radiosensitivity, Furthermore, overexpression of Bcl-xl occurs only in p53- lines and is associated with resistance to IR-induced apoptosis in these lines, indicating differential expression and regulation of Bcl-2 and Bcl-xl in p{\'e}diatrie ALL.",
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