Clinical significance of p53 mutations in relapsed T-cell acute lymphoblastic leukemia.
Clinical significance of p53 mutations in relapsed T-cell acute lymphoblastic leukemia.
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DOI：
10.1182/blood.v84.9.3105.bloodjournal8493105
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发表时间：
1994-11
期刊：
影响因子：
20.3
通讯作者：
M. Diccianni;Jennifer C. Yu;M. Hsiao;S. Mukherjee;Shaohua Le;A. Yu
中科院分区：
文献类型：
--
作者：
M. Diccianni;Jennifer C. Yu;M. Hsiao;S. Mukherjee;Shaohua Le;A. Yu
在t细胞急性淋巴细胞白血病（T-ALL）中，51例首次复发患者中有12例（24%）发现p53基因突变。在一项回顾性研究中，12例p53突变复发患者中有9例在诊断时获得骨髓样本；只有一名患者在诊断时发现p53突变。在18个未配对诊断的T-ALL样本中未发现进一步的p53突变。这是首次报道T-ALL诊断时p53突变。p53突变在复发性T-ALL中具有临床相关性。有p53突变的患者比没有p53突变的患者生存时间短。此外，与没有p53突变的患者相比，p53突变的患者通过再诱导治疗获得第二次完全缓解的可能性要小得多，即使获得了第二次再诱导，复发后的生存时间也更短。虽然p53突变主要是在复发时发现的，但它也与首次缓解持续时间缩短和诊断后总体生存率下降有关。p53突变患者的死亡风险比没有p53突变的患者高3.8倍。这些发现表明p53突变与临床预后差有关，其特点是：(1)首次复发后生存时间缩短；(2)对再诱导治疗的反应降低；（三）首次缓解时间缩短；因此，(4)总体上减少了生存时间，增加了死亡风险。
In T-cell acute lymphoblastic leukemia (T-ALL), p53 gene mutations were found in 12 of 51 patients in first relapse (24%). In a retrospective study, bone marrow samples at diagnosis were obtained from 9 of the 12 relapsed patients with p53 mutation; only one patient was found to harbor a p53 mutation at diagnosis. No further p53 mutations were identified in 18 unpaired diagnosis T-ALL samples. This is the first report of a p53 mutation in T-ALL at diagnosis. p53 mutations in relapsed T-ALL were clinically relevant. Patients with p53 mutations experience a shorter duration of survival than those patients without p53 mutations. Additionally, patients with p53 mutations were significantly less likely to have achieved a complete second remission from reinduction therapy than those patients without p53 mutations and experience a shorter duration of survival from relapse even when a second reinduction is obtained. Though primarily identified only at relapse, p53 mutations were also associated with a decreased duration of first remission and overall decrease in survival from diagnosis. Patients with p53 mutations had a 3.8-fold increase in risk of death than those patients without p53 mutations. These findings suggest that p53 mutation is associated with poor clinical outcome that is characterized by (1) a shortened duration of survival after first relapse; (2) a reduced response to reinduction therapy; (3) a shortened duration of first remission; and, hence, (4) an overall decreased duration of survival and increased risk of death.