The nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse model of childhood acute lymphoblastic leukemia reveals intrinsic differences in biologic characteristics at diagnosis and relapse
The nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse model of childhood acute lymphoblastic leukemia reveals intrinsic differences in biologic characteristics at diagnosis and relapse
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DOI：
10.1182/blood.v99.11.4100
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发表时间：
2002-06-01
期刊：
影响因子：
20.3
通讯作者：
Rice, AM
中科院分区：
文献类型：
--
作者：
Lock, RB;Liem, N;Rice, AM
将19例儿童急性淋巴细胞白血病细胞移植到非肥胖型糖尿病/严重联合免疫缺陷(NOD/SCID)小鼠体内，其中7例仍处于首次完全缓解(CR1)状态。骨髓、脾和肝脏均有高水平的浸润性改变，其他器官也有不同程度的浸润性改变。与原始患者样本相比，异种移植的免疫表型基本没有改变。此外，对整个p53编码区的测序显示，14例异种移植中有14例没有突变(10例来自确诊患者，4例复发)。从移植小鼠的脾中获取的细胞很容易将白血病转移到第二和第三受体。为了将异种移植的生物学特征与患者的临床和预后特征相关联，分析了单个白血病样本移植到NOD/SCID小鼠的比率。不同疾病阶段的生物学相关性不同：在复发时采集的样本中，植入率和CRI长度之间存在直接相关性(r=0.96；P=0.002)，但与诊断无关(r=0.38；P=0.40)。相反，6个异种移植物对长春新碱的体内反应显示，CR1的长度与长春新碱治疗后白血病细胞群恢复率之间存在直接相关(r=0.96；P=0.002)，无论异种移植物是来自初诊患者还是复发患者。这项研究支持了先前的发现，即儿童的NOD/SCID模型提供了对人类疾病的准确描述，并表明以患者特有的方式预测复发和设计替代治疗策略可能是有价值的。(C)2002年，由美国血液病学会公布。
Acute lymphoblastic leukemia cells from 19 children, including 7 who remain in first complete remission (CR1), were engrafted into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. High-level infiltration of bone marrow, spleen, and liver was observed, with variable infiltration of other organs. The Immunophenotypes of xenografts were essentially unaltered compared with the original patient sample. In addition, sequencing of the entire p53 coding region revealed no mutations in 14 of 14 xenografts (10 from patients at diagnosis and 4 at relapse). Cells harvested from the spleens of engrafted mice readily transferred the leukemia to secondary and tertiary recipients. To correlate biologic characteristics of xenografts with clinical and prognostic features of the patients, the rates at which individual leukemia samples engrafted in NOD/SCID mice were analyzed. Differences In biologic correlates were encountered depending on stage of disease: a direct correlation was observed between the rate of engraftment and length of CRI for samples harvested at relapse (r = 0.96; P = .002), but not diagnosis (r = 0.38; P = .40). In contrast, the in vivo responses of 6 xenografts to vincristine showed a direct correlation (r = 0.96; P = .002) between the length of CR1 and the rate at which the leukemia cell population recovered following vincristine treatment, regardless of whether the xenografts were derived from patients at diagnosis or relapse. This study supports previous findings that the NOD/SCID model of childhood ALL provides an accurate representation of the human disease and Indicates that It may be of value to predict relapse and design alternative treatment strategies In a patient-specific manner. (C) 2002 by The American Society of Hematology.