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To determine the role of the BCR-ABL gene in the proliferation of blast cells of patients with chronic myelogenous leukemia, leukemia blast cells were exposed to synthetic 18-mer oligodeoxynucleotides complementary to two identified BCR-ABL junctions. Leukemia colony formation was suppressed, whereas granulocyte-macrophage colony formation from normal marrow progenitors was unaffected. When equal proportions of normal marrow progenitors and blast cells were mixed, exposed to the oligodeoxynucleotides, and assayed for residual colony formation, the majority of residual cells were normal. These findings demonstrate the requirement for a functional BCR-ABL gene in maintaining the leukemic phenotype and the feasibility of gene-targeted selective killing of neoplastic cells.

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The process of cell loss and cell gain is homeostatically balanced in order to not only generate and maintain the complex dynamic architecture of tissues, but also to allow adaptation to changing circumstances. Tumor cells survive only by virtue of mutations that allow them to proliferate and to evade death signals. In fact, defects in the programd cell death inducing pathways contribute to neoplastic transformation, progression and metastasis by creating a permissive environment for genetic instability and accumulation of gene mutation. Resistance to apoptosis can also enhance the escape to tumor cells from surveillance by the immune system. Moreover, because chemotherapy and irradiation act mostly by inducing apoptosis, dysregulation in the apoptostic pathway can make cancer cells resistant to therapy. This review gives an update on the key players involved in apoptosis as well as how pathologic alterations in each step of apoptotic pathways are involved in the entire progression of neoplastic transformation, how impaired apoptosis affects therapy and how direct targeting vs. the apoptotic regulators could lead to more effective treatment of cancer.