Preudhomme C, Fenaux P
Laboratoire d'Hématologie A, CHRU Hôpital Calmette, Lille, France.
Pathol Biol (Paris). 1997 Dec;45(10):898-908.
Alterations in the p53 gene are less common in hematological malignancies (10 to 15%) than in solid tumors, and usually consist in point mutations, which can be readily detected using SSCP or ICC. In most cases (except in non-Hodgkin's lymphoma) there is a close correlation between point mutations and a positive ICC. In myelodysplastic syndromes, acute myeloid leukemia, chronic myeloid leukemia, and chronic lymphoid leukemia, point mutations affecting one allele are accompanied with deletion of the other allele. The complete absence of the p53 gene in these conditions probably explains the poor prognosis and resistance to chemotherapy in these patients. In contrast, in the L3 form of acute lymphoid leukemia and Burkitt's non-Hodgkin's lymphoma, punctual mutations are common (30%) and rarely accompanied with deletion of 17p. These data confirm the key role of p53 in the induction of apoptosis after chemotherapy and support the need for developing tools for transferring the p53 gene into malignant cells with the goal of restoring chemosensitivity.
与实体瘤相比，p53基因改变在血液系统恶性肿瘤中较少见（10%至15%），且通常为点突变，可通过单链构象多态性（SSCP）或免疫细胞化学（ICC）轻易检测到。在大多数情况下（非霍奇金淋巴瘤除外），点突变与ICC阳性密切相关。在骨髓增生异常综合征、急性髓系白血病、慢性髓系白血病和慢性淋巴细胞白血病中，影响一个等位基因的点突变伴随着另一个等位基因的缺失。在这些情况下p53基因完全缺失可能解释了这些患者预后不良和对化疗耐药的原因。相比之下，在急性淋巴细胞白血病的L3型和伯基特非霍奇金淋巴瘤中，点突变很常见（30%），很少伴有17p缺失。这些数据证实了p53在化疗后诱导细胞凋亡中的关键作用，并支持开发将p53基因导入恶性细胞以恢复化疗敏感性的工具的必要性。
