Expression of Apoptosis‐regulating Proteins Bcl‐2 and Bax in Lymph Node Aspirates from Dogs with Lymphoma

Abstract

BackgroundDysregulated apoptosis is a hallmark of tumorigenesis, and is also involved in resistance to cytotoxic treatment, and might be relevant in lymphoma in dogs.Hypothesis/ObjectivesThat Bcl‐2/Bax expression patterns differ between lymphoma immunophenotypes, and that Bcl‐2/Bax ratio is correlated with prognosis.AnimalsFifty‐five client‐owned dogs with multicentric lymphoma and 5 healthy dogs.MethodsProspective, case–control study. We compared 3 methods (flow cytometry, qRT‐PCR, Western blot) for Bcl‐2 and Bax quantification in a subset of dogs. The effect of time on Bcl‐2/Bax ratios measured by flow cytometry was assessed in lymphoma cell lines. Immunophenotype and Bcl‐2/Bax expression by flow cytometry were determined in LN aspirates from all dogs with multicentric lymphoma compared to healthy dogs. Progression‐free survival (PFS) was retrospectively evaluated in a group of dogs all receiving similar treatment.ResultsBcl‐2/Bax ratios remain consistent for at least 5 days after sample collection. Bcl‐2/Bax ratio was higher in dogs with T‐cell lymphoma (TCL; median 0.97, range 0.37–1.36) compared to B‐cell lymphoma (BCL; median 0.36, range 0.07–1.45) (P < .0001) and normal dogs (median 0.36, range 0.21–0.48) (P = .0006), respectively. Dogs with Bcl‐2/Bax ratios higher than the median of the group experienced a median PFS of 101 days and dogs with ratios equal and lower than the median had PFS of 130 days (P = .19).Conclusions and clinical importanceHigher intrinsic resistance to apoptosis following cytotoxic treatment might contribute to the less favorable prognosis associated with multicentric TCL in dogs. Whether Bcl‐2/Bax will be helpful to identify canine BCL and TCL with more aggressive and more indolent behavior, respectively, should be evaluated in larger prospective clinical studies.

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“…The Bcl-2 family is a major contributor to a large family of apoptotic proteins, including proteins that promote apoptosis, such as Bad, Bak and Bax, and proteins that inhibit apoptosis, such as Bcl-xl and Bcl-2 [44]. Cell fate is determined by the modulation of these two types of Bcl-2 family members [45]. To explore whether the promotion of PI3K/Akt signalling after TAS treatment helps to maintain cell viability through regulating the level of Bcl-2 family proteins, the levels of apoptosis-blocking members and the apoptosis-inducing element Bax were determined.…”

Electrochemotherapy induces tumor regression and decreases the proliferative index in canine cutaneous squamous cell carcinoma

“…BAX/Bcl-2 cross-regulation controls apoptosis, cell survival and cell proliferation 23,24 . Several studies have measured the expression of a single apoptosis-associated protein, such as BAX and BCL-2, by immunohistochemistry, flow cytometry or quantitative real-time PCR analyses and correlated its expression with the prognosis of mammary tumors and lymphoma 25–29 . However, conflicting data have been observed among the studies 25–27 .…”

Luteolin inhibits multi-heavy metal mixture-induced HL7702 cell apoptosis through downregulation of ROS-activated mitochondrial pathway

“…Bcl-2 and Bax are proteins belonging to the Bcl-2 family and control the mitochondrial membrane permeability to regulate the release of cytochrome c ( 45 ). Bax upregulates the permeability of the mitochondrial membrane accompanied with the release of cytochrome c from the mitochondria into the cytosol, while Bcl-2 has the opposite role ( 45 , 49 ). Cytochrome c in the cytosol activates caspase family proteins and forms the cytochrome c /Apaf1/caspase-9 apoptosome, which then leads to apoptosis ( 50 ).…”