Bcl-2 regulatory pathway is functional in chronic lymphocytic leukemia

Charles Goolsby*, Mary Paniagua, Martin Tallman, Ronald B. Gartenhaus

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Background: Chronic lymphocytic leukemia (CLL) is characterized by accumulation of clonal, malignant CD5+, CD23+ B cells. In vivo, these cells have an antiapoptotic phenotype (high levels of Bcl-2 and low levels of proapoptotic Bcl-2 family proteins, such as Bax). Abnormal B cells accumulate due to altered apoptosis regulation rather than to increased proliferation. However, it is unclear whether there are inherent Bcl-2 apoptotic pathway defects. With in vitro culture, these B cells rapidly apoptosis. Methods: To investigate apoptosis regulation, Bcl-2, Bax, mitochondrial membrane potential, annexin V, and caspase activation were simultaneous monitored in individual cells during in vitro apoptosis. Results: With in vitro culture, 30% to 50% of B cells were apoptotic at 24 h compared with fewer than 10% of T cells. Apoptotic B cells showed dramatic Bax upregulation and slight Bcl-2 decreases accompanied by decreased mitochondrial membrane potential and increased activated caspase-3 protein levels. Caspase-3 and caspase-9 activities were increased 18- to 51 -fold and 6- to 11 -fold, respectively, after 24 h of culture. Caspase-8 showed limited or no activation (less than fourfold). Conclusions: These data show that in vitro apoptosis of CLL B cells occurs through a well-characterized Bcl-2 regulatory pathway consistent with that pathway being functional. Further, these cells' antiapoptotic phenotype is dependent on the in vivo environment, potentially involving paracrine/autocrine interactions.

Original languageEnglish (US)
Pages (from-to)36-46
Number of pages11
JournalCytometry Part B - Clinical Cytometry
Volume63
Issue number1
DOIs
StatePublished - Jan 2005

Keywords

  • Apoptosis
  • B chronic lymphocytic leukemia
  • Bax
  • Bcl-2
  • Caspase activation
  • Flow cytometry

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

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