Electronic Resource
The Runx-PU.1 pathway preserves normal and AML/ETO9a leukemic stem cells
| العنوان: | The Runx-PU.1 pathway preserves normal and AML/ETO9a leukemic stem cells |
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| المؤلفون: | Staber, P.B. (Philipp), Zhang, P., Ye, M. (Min), Welner, R.S. (Robert), Levantini, E. (Elena), Di Ruscio, A. (Annalisa), Ebralidze, A. (Alexander), Bach, C.S. (Christian), Zhang, H. (Hong), Zhang, J. (Junyan), Vanura, K. (Katrina), Delwel, H.R. (Ruud), Yang, H. (Henry), Huang, G. (Gang), Tenen, D.G. (Daniel) |
| بيانات النشر: | 2014-10-09 |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Runx transcription factors contribute to hematopoiesis and are frequently implicated in hematologic malignancies. All three Runx isoforms are expressed at the earliest stages of hematopoiesis; however, their function in hematopoietic stem cells (HSCs) is not fully elucidated. Here, we show that Runx factors are essential in HSCs by driving the expression of the hematopoietic transcription factor PU.1. Mechanistically, by using a knockin mouse model in which all three Runx binding sites in the - 14kb enhancer of PU.1 are disrupted, we observed failure to form chromosomal interactions between the PU.1 enhancer and its proximal promoter. Consequently, decreased PU.1 levels resulted in diminished long-term HSC function through HSC exhaustion, which could be rescued by reintroducing a PU.1 transgene. Similarly, in a mouse model of AML/ETO9a leukemia, disrupting the Runx binding sites resulted in decreased PU.1 levels. Leukemia onset was delayed, and limiting dilution transplantation experiments demonstrated functional loss of leukemia-initiating cells. This is surprising, because low PU.1 levels have been considered a hallmark of AML/ETO leukemia, as indicated in mouse models and as shown here in samples from leukemic patients. Our data demonstrate that Runx-dependent PU.1 chromatin interaction and transcription of PU.1 are essential for both normal and leukemia stem cells. |
| مصطلحات الفهرس: | info:eu-repo/semantics/article |
| DOI: | 10.1182.blood-2014-01-550855 |
| URL: | |
| الاتاحة: | Open access content. Open access content info:eu-repo/semantics/openAccess |
| ملاحظة: | Blood vol. 124 no. 15, pp. 2391-2399 English |
| Other Numbers: | QGQ oai:repub.eur.nl:87281 doi:10.1182/blood-2014-01-550855 urn:hdl:1765/87281 957103696 |
| المصدر المساهم: | ERASMUS UNIVERSITEIT ROTTERDAM From OAIster®, provided by the OCLC Cooperative. |
| رقم الانضمام: | edsoai.ocn957103696 |
| قاعدة البيانات: | OAIster |
| DOI: | 10.1182.blood-2014-01-550855 |
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