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老年新西兰黑鼠淋巴细胞增生性疾病的自然病史。

The natural history of a lymphoproliferative disorder in aged NZB mice.

作者信息

Marti G E, Metcalf R A, Raveche E

机构信息

Section of Flow and Image Cytometry, Food and Drug Administration, NIH, Bethesda, MD 20892.

出版信息

Curr Top Microbiol Immunol. 1995;194:117-26. doi: 10.1007/978-3-642-79275-5_15.

DOI:10.1007/978-3-642-79275-5_15
PMID:7895486
Abstract

The molecular lesions of human familial and common B-CLL remain unknown. As an approach to this problem, aged NZB mice with a B cell lymphoproliferative disorder were chosen as a murine model. Three groups of NZB mice (2 months, 6 months and > 18 months) for a total of nineteen were studied. A complete autopsy including a CBC was performed on each mouse. Spleen cells were immunophenotyped and cell cycle analysis was performed. Spleen weight, peritoneal cell counts and absolute lymphocytes counts were all elevated in the oldest group. All mice showed evidence of extramedulary hematopoiesis and the older group showed lymphocytic infiltrates in the lacrymal glands, kidneys, liver and lungs. Two of the seven aged mice had a malignant lymphoma. One was a marginal zone lymphoma and the other a lymphocytic lymphoma. Splenic immunophenotyping showed a loss of T cells with an increase in B cells as the mice age. Cell cycle analysis revealed hyperdiploidy in all of the aged mice with a decrease in the percentage G0G1 cells. This disease appears to involve an absolute lymphocytosis of the peritoneum and the peripheral blood compartment. This is associated with splenic aneuploidy. The infiltration of the spleen by malignant cells of varying morphology is a late event. The aged NZB mouse continues to be a model for human B-CLL.

摘要

人类家族性和常见B细胞慢性淋巴细胞白血病(B-CLL)的分子损伤仍不清楚。作为解决这个问题的一种方法,选择患有B细胞淋巴增殖性疾病的老年新西兰黑鼠(NZB)作为小鼠模型。研究了三组共19只NZB小鼠(2个月、6个月和大于18个月)。对每只小鼠进行了包括全血细胞计数(CBC)在内的完整尸检。对脾细胞进行了免疫表型分析并进行了细胞周期分析。最老的一组小鼠的脾脏重量、腹腔细胞计数和绝对淋巴细胞计数均升高。所有小鼠均有髓外造血的证据,且老年组在泪腺、肾脏、肝脏和肺中出现淋巴细胞浸润。7只老年小鼠中有2只患有恶性淋巴瘤。一只是边缘区淋巴瘤,另一只是淋巴细胞淋巴瘤。脾脏免疫表型分析显示,随着小鼠年龄增长,T细胞减少而B细胞增加。细胞周期分析显示所有老年小鼠均为超二倍体,G0G1期细胞百分比降低。这种疾病似乎涉及腹膜和外周血区室的绝对淋巴细胞增多。这与脾脏非整倍体有关。形态各异的恶性细胞浸润脾脏是一个晚期事件。老年NZB小鼠仍然是人类B-CLL的模型。

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引用本文的文献

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Abnormal microRNA-16 locus with synteny to human 13q14 linked to CLL in NZB mice.与人类13q14存在同线性的异常微小RNA - 16基因座与新西兰黑小鼠的慢性淋巴细胞白血病相关。
Blood. 2007 Jun 15;109(12):5079-86. doi: 10.1182/blood-2007-02-071225. Epub 2007 Mar 9.
2
BAFF and APRIL support chronic lymphocytic leukemia B-cell survival through activation of the canonical NF-kappaB pathway.B细胞活化因子(BAFF)和增殖诱导配体(APRIL)通过激活经典的核因子κB(NF-κB)信号通路来维持慢性淋巴细胞白血病B细胞的存活。
Blood. 2007 Jan 15;109(2):703-10. doi: 10.1182/blood-2006-06-027755. Epub 2006 Sep 14.