CREB: A Key Regulator of Normal and Neoplastic Hematopoiesis.
CREB: A Key Regulator of Normal and Neoplastic Hematopoiesis.
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DOI：
10.1155/2009/634292
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发表时间：
2009
影响因子：
--
通讯作者：
Sakamoto KM
中科院分区：
文献类型：
--
作者：
Sandoval S;Pigazzi M;Sakamoto KM
cAMP反应元件结合蛋白（CREB）是细胞表面受体和有丝分裂原下游的核转录因子，对正常和肿瘤性造血至关重要。我们实验室以前的工作表明，大多数急性髓性白血病（AML）和急性淋巴细胞白血病（ALL）患者的骨髓中过表达CREB。为了了解CREB在白血病发生中的作用，我们研究了CREB过表达对原代白血病细胞、白血病细胞系和CREB过表达转基因小鼠的生物学效应。我们的研究结果表明，CREB过表达导致细胞增殖和存活的增加。此外，CREB转基因小鼠在骨髓和脾脏中发展出异常骨髓生成的骨髓增殖性疾病。来自其他研究组的额外研究表明，cAMP早期诱导型阻遏物（ICER）（一种CREB阻遏物）的表达在白血病中也是失调的。而且，miR-34 b，一种负调节CREB表达的microRNA，与健康骨髓相比，在髓性白血病细胞系中的表达水平较低。总之，这些数据表明CREB在细胞转化中起作用。这些数据还表明，CREB特异性信号通路可能作为治疗干预的潜在靶点。
The cAMP response element-binding protein (CREB) is a nuclear transcription factor downstream of cell surface receptors and mitogens that is critical for normal and neoplastic hematopoiesis. Previous work from our laboratory demonstrated that a majority of patients with acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) overexpress CREB in the bone marrow. To understand the role of CREB in leukemogenesis, we examined the biological effect of CREB overexpression on primary leukemia cells, leukemia cell lines, and CREB overexpressing transgenic mice. Our results demonstrated that CREB overexpression leads to an increase in cellular proliferation and survival. Furthermore, CREB transgenic mice develop a myeloproliferative disorder with aberrant myelopoiesis in both the bone marrow and spleen. Additional research from other groups has shown that the expression of the cAMP early inducible repressor (ICER), a CREB repressor, is also deregulated in leukemias. And, miR-34b, a microRNA that negative regulates CREB expression, is expressed at lower levels in myeloid leukemia cell lines compared to that of healthy bone marrow. Taken together, these data suggest that CREB plays a role in cellular transformation. The data also suggest that CREB-specific signaling pathways could possibly serve as potential targets for therapeutic intervention.