Increased expression levels of the
Oct-1 transcription factor is considered to be one of the key markers of poor
cancer prognosis. In addition to the ubiquitous Oct-1A
isoform, which is found in all cells, there also exists a tissue-specific Oct-1L
isoform, which is expressed in hematopoietic cells. Oct-1L increases cell resistance to different stresses and also regulates the expression of genes controlling differentiation of hematopoietic and immune system cells. The tissue-specific Oct-1L
isoform levels are significantly increased in the B-cell lymphoblastoma Namalwa and Raji lines and the T-cell lymphoblastoma Jurkat line compared to normal B and T cells. Apparently, aberrant Oct-1L overexpression not only enhances stress resistance but also leads to the disruption of developmental pathways in the cells promoting their malignant transformation. We report here that targeted suppression of the tissue-specific Oct-1L
isoform expression reduces the proliferation rate of Namalwa B-lymphoblastic
Burkitt's lymphoma cells, significantly increases cell death rate under hypoxic conditions, and makes cells more sensitive to chemotherapeutic agents such as
docetaxel and
doxorubicin. These results indicate that targeted
therapy aimed at the suppression of the Oct-1
isoforms with increased expression levels in
tumor cells rather than the total Oct-1, thus avoiding the traumatic effects of total Oct-1 knockdown, may be promising. Selective suppression of Oct-1
isoforms is a promising strategy in the treatment of lymphoid
tumors and may contribute to mitigating the disease course and increasing survival rates in
cancer patients.