Differential requirements for c-Myc in chronic hematopoietic hyperplasia and acute hematopoietic malignancies in Pten-null mice.
Differential requirements for c-Myc in chronic hematopoietic hyperplasia and acute hematopoietic malignancies in Pten-null mice.
复制标题
作者：
骨髓增生性疾病（MPD）、淋巴增生性疾病（LPD）、急性T淋巴细胞性或髓样白血病和T淋巴细胞性淋巴瘤在诱导型Pten敲除（Pten−/−）小鼠中发生。这些多种疾病在一个动物模型中的出现为同时研究多种疾病的发病机制提供了机会。为了研究Myc功能是否是Pten−/−小鼠中这些造血疾病发展所必需的，我们产生了诱导型Pten/Myc双敲除小鼠（Pten−/−/Myc−/−）。通过比较这些双敲除小鼠与Pten−/−小鼠的造血表型，我们发现两组动物都发生了MPD和LPD。然而，没有化合物突变小鼠发生急性白血病或淋巴瘤。有趣的是，与Pten−/−小鼠中由粒细胞主导的MPD相反，巨核细胞在Pten−/−/Myc−/−小鼠的MPD中占主导地位。我们的研究表明，Pten−/−造血细胞中PI 3 K/Akt信号的失调保护这些细胞免于凋亡性细胞死亡，导致慢性增殖性疾病。但由于粒细胞与巨核细胞增殖相比对Myc的需求不同，Myc缺失将Pten−/− MPD从粒细胞主导转化为巨核细胞主导。Myc是急性造血系统恶性肿瘤发展所必需的。
Myeloproliferative disorders (MPDs), lymphoproliferative disorders (LPDs), acute T-lymphocytic or myeloid leukemia and T-lymphocytic lymphoma were developed in inducible Pten-knockout (Pten−/−) mice. The appearance of these multiple diseases in one animal model provides an opportunity to study the pathogenesis of multiple diseases simultaneously. To study whether Myc function is required for the development of these hematopoietic disorders in Pten−/− mice, we generated inducible Pten/Myc double-knockout mice (Pten−/−/Myc−/−). By comparing the hematopoietic phenotypes of these double-knockout mice with those of Pten−/− mice, we found that both sets of animals developed MPDs and LPDs. However, none of the compound-mutant mice developed acute leukemia or lymphoma. Interestingly, in contrast to the MPDs which developed in Pten−/− mice which are dominated by granulocytes, megakaryocytes predominate in the MPDs of Pten−/−/Myc−/− mice. Our study suggests that the deregulation of PI3K/Akt signaling in Pten−/− hematopoietic cells protects these cells from apoptotic cell death, resulting in chronic proliferative disorders. But due to the differential requirement for Myc in granulocyte as compared to megakaryocyte proliferation, Myc deletion converts Pten−/− MPDs from granulocyte-dominated to megakaryocyte-dominated conditions. Myc is absolutely required for the development of acute hematopoietic malignancies.
登录
查看更多内容
影响因子：
30.5
作者：
Douglas, NC;Jacobs, H;Hayday, AC
通讯作者：
Hayday, AC
DOI：
10.1073/pnas.201167798
发表时间：
2001-09-25
影响因子：
11.1
作者：
Kwabi-Addo, B;Giri, D;Ittmann, M
通讯作者：
Ittmann, M
影响因子：
158.5
作者：
Jamieson, CHM;Ailles, LE;Weissman, IL
通讯作者：
Weissman, IL
影响因子：
8
作者：
Hoffman, B;Amanullah, A;Liebermann, DA
通讯作者：
Liebermann, DA
影响因子：
11.4
作者：
Hu, Y.;Chen, Y.;Li, S.
通讯作者：
Li, S.