Lotem J, Sachs L
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Leukemia. 1996 Jun;10(6):925-31.
Hematopoietic cells require certain cytokines including colony-stimulating factors and interleukins to maintain viability. Without these cytokines the program of apoptotic cell death is activated. Cells from many myeloid leukemias require cytokines for viability, and apoptosis is also activated in these leukemic cells after cytokine withdrawal resulting in reduced leukemogenicity. The same cytokines protect normal and leukemic cells from induction of apoptosis by irradiation and cytotoxic chemotherapeutic compounds. This suggests that decreasing the levels of viability inducing cytokines may increase the effectiveness of cytotoxic anti-cancer therapy. The susceptibility of normal and cancer cells to induction of apoptosis is also regulated by the balance between apoptosis-inducing genes such as the tumor suppressor wild-type p53, and c-myc and bax, and apoptosis-suppressing genes such as the oncogene mutant p53, and bcl-2 and bcl-XL. Cell susceptibility to induction of apoptosis in leukemic cells could be enhanced by increased expression of apoptosis-inducing genes and/or decreased expression of apoptosis-suppressing genes. Modulation of expression of apoptosis-regulating genes should thus also be useful for improvement of anti-cancer therapy.
造血细胞需要某些细胞因子，包括集落刺激因子和白细胞介素，以维持生存能力。没有这些细胞因子，凋亡性细胞死亡程序就会被激活。许多髓系白血病的细胞需要细胞因子来维持生存能力，在撤除细胞因子后，这些白血病细胞也会激活凋亡，从而降低致白血病性。同样的细胞因子可保护正常细胞和白血病细胞免受辐射和细胞毒性化疗化合物诱导的凋亡。这表明降低维持生存能力的细胞因子水平可能会提高细胞毒性抗癌治疗的效果。正常细胞和癌细胞对凋亡诱导的敏感性也受凋亡诱导基因（如肿瘤抑制因子野生型p53、c-myc和bax）与凋亡抑制基因（如癌基因突变型p53、bcl-2和bcl-XL）之间平衡的调节。白血病细胞对凋亡诱导的敏感性可通过增加凋亡诱导基因的表达和/或降低凋亡抑制基因的表达来增强。因此，调节凋亡调控基因的表达对于改善抗癌治疗也应该是有用的。
