Pendergrass T W
Semin Oncol. 1985 Jun;12(2):80-91.
Although the etiology of acute leukemia is largely unknown, some facets of the puzzle are becoming clarified. Recognition of important patterns in age-specific mortality rates has suggested that events early in life, perhaps even prenatally, may have an influence on developing leukemia in childhood. The racial differences evident in mortality, incidence, and immunologic subtype of ALL suggest either differences in exposures to certain "factors" or differences in responses to those "factors" by white children. Hereditary factors appear to play a role. Familial and hereditary conditions exist that have high incidences of acute leukemia. Chromosomal anomalies are common in these conditions. Viral infections may play a role by contributing to alteration in genetic material through incorporation of the viral genome. How that virus is dealt with after primary infection seems important. The presence of immunodeficiency may allow wider dissemination or enhanced replication of such viruses, thereby increasing the likelihood of cellular transformation to an abnormal cell. Proliferation of that malignant cell to a clone may depend on other cofactors. Perhaps prolonged exposure to substances like benzene or alkylating agents may enhance these interactions between virus and genetic material. Does this change DNA repair mechanisms? Are viral infections handled differently? Is viral genomic information more easily integrated into host cells? Ionizing radiation has multiple effects. Alteration in genetic material occurs both at the molecular and chromosomal levels. DNA may be altered, lost, or added in the cell's attempt to recover from the injury. These changes may lead to altered susceptibility to other environmental agents, and host response may be altered. The past 40 years have seen dramatic progress in the treatment of ALL. We have just begun to unravel the complex interactions of genetic makeup, immune response, and the environment on the development of ALL. Whether factors can be identified that may allow prevention of acute leukemia remains to be seen.
尽管急性白血病的病因在很大程度上尚不清楚，但谜团的一些方面正逐渐明晰。对特定年龄死亡率重要模式的认识表明，生命早期甚至可能在出生前发生的事件，可能会对儿童期白血病的发生产生影响。急性淋巴细胞白血病（ALL）在死亡率、发病率和免疫亚型方面明显的种族差异，表明白人儿童在接触某些“因素”方面存在差异，或者对这些“因素”的反应存在差异。遗传因素似乎发挥了作用。存在家族性和遗传性疾病，其急性白血病发病率很高。染色体异常在这些疾病中很常见。病毒感染可能通过将病毒基因组整合到遗传物质中，导致遗传物质改变，从而发挥作用。初次感染后病毒如何被处理似乎很重要。免疫缺陷的存在可能使此类病毒更广泛地传播或增强复制，从而增加细胞转化为异常细胞的可能性。该恶性细胞增殖形成克隆可能取决于其他辅助因素。也许长期接触苯或烷化剂等物质可能会增强病毒与遗传物质之间的这些相互作用。这会改变DNA修复机制吗？病毒感染的处理方式会有所不同吗？病毒基因组信息是否更容易整合到宿主细胞中？电离辐射有多种影响。遗传物质在分子和染色体水平都会发生改变。细胞试图从损伤中恢复时，DNA可能会被改变、丢失或添加。这些变化可能导致对其他环境因素的易感性改变，并且宿主反应可能会改变。在过去40年里，ALL的治疗取得了巨大进展。我们才刚刚开始揭示基因组成、免疫反应和环境在ALL发生发展过程中的复杂相互作用。是否能确定可预防急性白血病的因素还有待观察。
