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The Role of Nadph Oxidase 2 in Myeloid Leukemia and Normal Hematopoiesis
Başlık:
The Role of Nadph Oxidase 2 in Myeloid Leukemia and Normal Hematopoiesis
Yazar:
Adane, Biniam, author.
ISBN:
9780438002814
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (149 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-10(E), Section: B.
Advisors: Craig T. Jordan Committee members: KATHRIN BERNT; JAMES DEGREGORI; HEIDE FORD; DANIEL POLLYEA.
Özet:
The hematopoietic oxidase NOX2 is an important effector of immune cell function and its activity has been linked to oncogenic signaling. Here, we describe a role for NOX2 in leukemia initiating stem cells (LSCs) and normal hematopoietic precursors. In a murine model of myeloid leukemia, deficiency of NOX2 attenuated disease development; reduced basal levels of ROS, abrogated stem cell associated transcriptional programs and ultimately induced terminal differentiation of leukemic blasts. Downstream of NOX2, we identified the transcription factor FOXC1 as a critical node controlling leukemogenesis.
In xenotransplantation models of primary human myeloid leukemia, suppression of either NOX2 or FOXC1 significantly attenuated disease development. Strikingly in normal settings, NOX2 is expressed by a subset of multipotent progenitors and in its absence increased number of myeloid cells are generated. Collectively these findings position NOX2 as a critical regulator of normal and malignant hematopoiesis and highlight the clinical potential of inhibiting NOX2 as a means to target LSCs.
Notlar:
School code: 1639
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(678290.1) | 678290-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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