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SRF/MRTFA Regulatory Axis: Its Role ...

Rahman, Nur-Taz.

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SRF/MRTFA Regulatory Axis: Its Role in Megakaryopoiesis and De-regulation in Acute Megakaryoblastic Leukemia.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	SRF/MRTFA Regulatory Axis: Its Role in Megakaryopoiesis and De-regulation in Acute Megakaryoblastic Leukemia./
作者:	Rahman, Nur-Taz.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
面頁冊數:	94 p.
附註:	Source: Dissertations Abstracts International, Volume: 81-03, Section: B.
Contained By:	Dissertations Abstracts International81-03B.
標題:	Cellular biology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13809842
ISBN:	9781088317136

SRF/MRTFA Regulatory Axis: Its Role in Megakaryopoiesis and De-regulation in Acute Megakaryoblastic Leukemia.
Rahman, Nur-Taz.

SRF/MRTFA Regulatory Axis: Its Role in Megakaryopoiesis and De-regulation in Acute Megakaryoblastic Leukemia. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 94 p.

Source: Dissertations Abstracts International, Volume: 81-03, Section: B.

Thesis (Ph.D.)--Yale University, 2019.

This item is not available from ProQuest Dissertations & Theses.

Megakaryopoiesis is the process by which hematopoietic stem cells (HSCs) in the bone marrow mature down the megakaryocytic lineage to give rise to large cells called megakaryocytes (Mks). Mks then give rise to platelets, which circulate in the blood to prevent excess loss of blood by clotting, and therefore, play a major role in hemostasis. In Acute Megakaryoblastic Leukemia (AMKL), megakaryopoiesis is blocked, the bone marrow is filled with blasts of the megakaryocytic lineage, and the patients suffer from thrombocytopenia. Multiple chromosomal translocations have been identified in AMKL patients, one of which is the t(1;22), which gives rise to the RBM15-MRTFA (RM) fusion protein. We know that the transcription factor Serum Response Factor (SRF) and its co-factor MRTFA (myocardin-related transcription factor A) are necessary for megakaryopoiesis, and that MRTFA over-expression augments the megakaryocytic characteristics. Our goal was to understand how SRF/MRTFA contributes to megakaryopoiesis, and whether regulation by SRF/MRTFA is hindered in AMKL. Our hypothesis was that SRF/MRTFA binding increases at key genomic sites during megakaryopoiesis, which upregulates important genes that promote Mk formation; and that this binding is abrogated in AMKL where MRTFA is also expressed as part of the RM fusion protein. We have been able to show increased SRF and MRTFA binding at important genomic sites during megakaryopoiesis in primary human Mks, show decreased SRF binding when RM is expressed, and identify PURB as a gene that may directly block Mk maturation in AMKL.

ISBN: 9781088317136Subjects--Topical Terms:

3172791
Cellular biology.
Subjects--Index Terms:

Genomic analysis

SRF/MRTFA Regulatory Axis: Its Role in Megakaryopoiesis and De-regulation in Acute Megakaryoblastic Leukemia.
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520 $a Megakaryopoiesis is the process by which hematopoietic stem cells (HSCs) in the bone marrow mature down the megakaryocytic lineage to give rise to large cells called megakaryocytes (Mks). Mks then give rise to platelets, which circulate in the blood to prevent excess loss of blood by clotting, and therefore, play a major role in hemostasis. In Acute Megakaryoblastic Leukemia (AMKL), megakaryopoiesis is blocked, the bone marrow is filled with blasts of the megakaryocytic lineage, and the patients suffer from thrombocytopenia. Multiple chromosomal translocations have been identified in AMKL patients, one of which is the t(1;22), which gives rise to the RBM15-MRTFA (RM) fusion protein. We know that the transcription factor Serum Response Factor (SRF) and its co-factor MRTFA (myocardin-related transcription factor A) are necessary for megakaryopoiesis, and that MRTFA over-expression augments the megakaryocytic characteristics. Our goal was to understand how SRF/MRTFA contributes to megakaryopoiesis, and whether regulation by SRF/MRTFA is hindered in AMKL. Our hypothesis was that SRF/MRTFA binding increases at key genomic sites during megakaryopoiesis, which upregulates important genes that promote Mk formation; and that this binding is abrogated in AMKL where MRTFA is also expressed as part of the RM fusion protein. We have been able to show increased SRF and MRTFA binding at important genomic sites during megakaryopoiesis in primary human Mks, show decreased SRF binding when RM is expressed, and identify PURB as a gene that may directly block Mk maturation in AMKL.
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