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The Balance of STAT5 and NFkappaB or IKAROS at Enhancer Networks Dictates Progenitor B Cell Survival, Proliferation, and Differentiation.

Record Type:	Language materials, manuscript : Monograph/item
Title/Author:	The Balance of STAT5 and NFkappaB or IKAROS at Enhancer Networks Dictates Progenitor B Cell Survival, Proliferation, and Differentiation./
Author:	Katerndahl, Casey Duncan Saul.
Description:	1 online resource (129 pages)
Notes:	Source: Dissertation Abstracts International, Volume: 79-04(E), Section: B.
Contained By:	Dissertation Abstracts International79-04B(E).
Subject:	Biology. -
Online resource:	click for full text (PQDT)
ISBN:	9780355405682

The Balance of STAT5 and NFkappaB or IKAROS at Enhancer Networks Dictates Progenitor B Cell Survival, Proliferation, and Differentiation.
Katerndahl, Casey Duncan Saul.

The Balance of STAT5 and NFkappaB or IKAROS at Enhancer Networks Dictates Progenitor B Cell Survival, Proliferation, and Differentiation. - 1 online resource (129 pages)

Source: Dissertation Abstracts International, Volume: 79-04(E), Section: B.

Thesis (Ph.D.)--University of Minnesota, 2015.

Includes bibliographical references

B cell Acute Lymphoblastic Leukemia (B-ALL) arises from transformation of progenitor B cells. The transcription factor STAT5 plays a critical role in B-ALL, as high STAT5 activation is correlated with poor patient survival. How STAT5 mediates this effect is unclear. Previous studies suggested that STAT5 simply promotes the survival of progenitor B cells. However, other roles for STAT5 in B-ALL have not been explored. This study demonstrates that STAT5 activation drives leukemia in cooperation with defects in a linear signaling pathway emanating from the pre-BCR, including Blnk, Btk, Prkcb, Nfkb1, and Ikaros. Using microarray analysis and chromatin immunoprecipitation followed by high throughput sequencing (ChIP-seq), we demonstrate that STAT5 antagonizes NF?B and IKAROS by opposing regulation of shared target genes. High levels of STAT5 binding was enriched at super-enhancers that are typically associated with an opposing network of B cell transcription factors including PAX5, EBF1, PU.1, IRF4, or IKAROS. The antagonism between STAT5 and NFkappaB or IKAROS has direct clinical relevance as the balance between these transcription factors affects patient outcome. Patients with high ratios of active STAT5 to NFkappaB or IKAROS have more aggressive disease characterized by decreased survival. Our studies illustrate how modest perturbations in two opposing transcriptional programs have dramatic consequences for B cell transformation, and that the degree of antagonism between these transcriptional programs correlates with patient survival.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2018

Mode of access: World Wide Web

ISBN: 9780355405682Subjects--Topical Terms:

599573
Biology.
Index Terms--Genre/Form:

554714
Electronic books.

The Balance of STAT5 and NFkappaB or IKAROS at Enhancer Networks Dictates Progenitor B Cell Survival, Proliferation, and Differentiation.
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504 $a Includes bibliographical references
520 $a B cell Acute Lymphoblastic Leukemia (B-ALL) arises from transformation of progenitor B cells. The transcription factor STAT5 plays a critical role in B-ALL, as high STAT5 activation is correlated with poor patient survival. How STAT5 mediates this effect is unclear. Previous studies suggested that STAT5 simply promotes the survival of progenitor B cells. However, other roles for STAT5 in B-ALL have not been explored. This study demonstrates that STAT5 activation drives leukemia in cooperation with defects in a linear signaling pathway emanating from the pre-BCR, including Blnk, Btk, Prkcb, Nfkb1, and Ikaros. Using microarray analysis and chromatin immunoprecipitation followed by high throughput sequencing (ChIP-seq), we demonstrate that STAT5 antagonizes NF?B and IKAROS by opposing regulation of shared target genes. High levels of STAT5 binding was enriched at super-enhancers that are typically associated with an opposing network of B cell transcription factors including PAX5, EBF1, PU.1, IRF4, or IKAROS. The antagonism between STAT5 and NFkappaB or IKAROS has direct clinical relevance as the balance between these transcription factors affects patient outcome. Patients with high ratios of active STAT5 to NFkappaB or IKAROS have more aggressive disease characterized by decreased survival. Our studies illustrate how modest perturbations in two opposing transcriptional programs have dramatic consequences for B cell transformation, and that the degree of antagonism between these transcriptional programs correlates with patient survival.
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