19q13.33

Various cancers and diseases

Colorectal cancer, T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia (CLL), B cell chronic lymphocytic leukemia, osteomyelitis.

BAX mutations have been found to be associated with positive prognosis in Dukes B2 patients, concerning survival.
The G(-248)A polymorphism in the promoter region of the BAX gene has been associated with reduced BAX expression, advanced disease stage, reduced treatment response and short overall survival in B-cell chronic lymphocytic leukemia (CLL).
Polymorphisms were found for BAX, caused by variation in nucleotide A repeat number at position 360 in the 5-region of BAX gene. These allelic frequencies of BAX polymorphism were significantly different between males and females and therefore associated with gender-based heamatocrite (HCT) differences.
Substitution of the nucleotide G-->A at position -248 in the BAX gene was more frequent in patients with osteomyelitis and was associated with a longer lifespan of their peripheral blood neutrophils, probably possessing a significant role in the pathogenesis of osteomyelitis.
In cases of malignancies, the concentration of BAX protein in cancer cells is reduced. In addition, p53- deficient mice show reduced BAX levels, ultimately developing T-cell lymphoma.
Reduction of BAX expression levels is negatively associated with many cancers outcome. It is associated with a variety of adverse prognostic factors such as poor response to radio- and chemotherapy, advanced stage, lymph node metastasis, and reduced disease-free and overall survival in variety cancer types, such as colorectal, pancreatic, breast, head and neck, prostate, small cell lung cancer and gynecological (ovarian) malignancies. More specifically, the enhanced expression of BAX protein is a positive prognostic factor for pancreatic cancer and sensitizes human pancreatic cancer cells to apoptosis induced by chemotherapeutic agents. In the case of stage II colon cancer, treated only with surgery, BAX protein expression may be a predictor for prognosis. In ovarian cancer, BAX protein may have a predictive potential in taxane-platinum-treated patients. Moreover, in resected non-small cell lung cancer, low expression of BAX implies poor prognosis. In addition, in patients with advanced esophageal cancer, treated with chemoradiotherapy, reduced expression levels of BAX predict poor prognosis. Low expression of BAX was also significantly associated with poor PFS and OS in nasopharyngeal cancer patients.
In lung cancer, BAX is translocated to the nucleus, enhancing tumour development. Furthermore, mutational analysis of the gene in cases of lung cancer patients revealed the presence of a silent point mutation in codon 184 (TCG>TCA), as well as intronic mutations.
In T cells and endometrium of patients with acute lymphoblastic leukaemia, frameshift mutations have been detected in the BAX gene.
It is a common observation in cases of gastrointestinal cancer, the detection of two specific missense mutations of the BAX gene in codon 169 (Thr > Ala or Thr > Met), which cause inhibition of the proapoptotic activity of the protein and enhance the development of cancer.
Various chemotherapeutic treatments act via up-regulation of the BAX gene to block tumour progression.
BAX is highly expressed in HL-60 but it was found to be hardly expressed in HL-CR cells, a C2-ceramide-resistant HL-60 subline, which has been recently established. These cells showed reduced response to a variety of anticancer drugs including ceramide, doxorubicin, etoposide and cytosine arabinoside.

Not identified so far.

Not identified so far.