Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice.
نویسندگان
چکیده
Chromosomal translocations involving the MALT1 gene are hallmarks of mucosa-associated lymphoid tissue (MALT) lymphoma. To date, targeting these translocations to mouse B cells has failed to reproduce human disease. Here, we induced MALT1 expression in mouse Sca1(+)Lin(-) hematopoietic stem/progenitor cells, which showed NF-κB activation and early lymphoid priming, being selectively skewed toward B-cell differentiation. These cells accumulated in extranodal tissues and gave rise to clonal tumors recapitulating the principal clinical, biological, and molecular genetic features of MALT lymphoma. Deletion of p53 gene accelerated tumor onset and induced transformation of MALT lymphoma to activated B-cell diffuse large-cell lymphoma (ABC-DLBCL). Treatment of MALT1-induced lymphomas with a specific inhibitor of MALT1 proteolytic activity decreased cell viability, indicating that endogenous Malt1 signaling was required for tumor cell survival. Our study shows that human-like lymphomas can be modeled in mice by targeting MALT1 expression to hematopoietic stem/progenitor cells, demonstrating the oncogenic role of MALT1 in lymphomagenesis. Furthermore, this work establishes a molecular link between MALT lymphoma and ABC-DLBCL, and provides mouse models to test MALT1 inhibitors. Finally, our results suggest that hematopoietic stem/progenitor cells may be involved in the pathogenesis of human mature B-cell lymphomas.
منابع مشابه
MALT lymphoma meets stem cells
Mucosa-associated lymphoid tissue (MALT) lymphomas are a distinct clinico-pathologic entity mainly associated with chromosomal translocations involving the MALT1 gene. Therefore, these chromosomal rearrangements have been traditionally used to identify tumor MALT lymphoma B-cells, and they have always been detected in differentiated tumoral B cells. However, the hematopoietic progenitor and ste...
متن کاملSpecification of Hemato-Endothelial-Like Structures and Generation of Hematopoietic Progenitor Cells from Human Pluripotent Stem Cells
Background and purpose: Human pluripotent stem cells (hPSCs) with the ability to differentiate into adult cells have provided a new perspective for treatment of some diseases. But, the efficiency of differentiation methods to generate hematopoietic progenitor cells (HPCs) is faced with multiple challenges. In the present study, we investigated the formation of hemato-endothelial-like structure...
متن کاملبررسی اثر آگونیست -آدرنرژیکی ایزوپروترنول بر بیان miR-886-3p و miR-23a در سلولهای بنیادی مزانشیمی مغز استخوان انسان
Background and Objective: Mobilization of Hematopoietic Stem Cells (HSCs) for transplantation and the importance of -adrenergic signals in induction of this process have been well investigated. However, little is known about the role of -adrenergic signals in mobilization of HSCs and factors influenced by these signals. The Chemokine Stromal Derived Factor -1 (SDF-1) which is expressed by hum...
متن کاملEffect of human amnion-derived multipotent progenitor cells on hematopoietic recovery after total body irradiation in C57BL/6 mice
Background: The hematopoietic system is sensitive to the adverse effects of ionizing radiation. Cellular therapies utilizing mesenchymal stem cells or vascular endothelial cells have been explored as potential countermeasures for radiation hematopoietic injuries. We investigated cells cultured from amnion ...
متن کاملA review of Biology and clinical use of Mesenchymal stem cell: an immune -modulator progenitor cell
Human mesenchymal stem cells (hMSCs), which also called mesenchymal stromal cells, are multipotent stem cell. Human MSCs typically are positive for the surface markers CD44, CD73, CD90, CD105, CD106, and also negative for hematopoietic markers CD34 and CD45.These cells can be isolated from postnatal bone marrow, adipose tissue, placenta, and scalp tissue, as well as from various fetal tissues. ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Proceedings of the National Academy of Sciences of the United States of America
دوره 109 26 شماره
صفحات -
تاریخ انتشار 2012