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Antagonism of B cell enhancer networks by STAT5 drives leukemia and poor patient survival.

Abstract：

:The transcription factor STAT5 has a critical role in B cell acute lymphoblastic leukemia (B-ALL). How STAT5 mediates this effect is unclear. Here we found that activation of STAT5 worked together with defects in signaling components of the precursor to the B cell antigen receptor (pre-BCR), including defects in BLNK, BTK, PKCβ, NF-κB1 and IKAROS, to initiate B-ALL. STAT5 antagonized the transcription factors NF-κB and IKAROS by opposing regulation of shared target genes. Super-enhancers showed enrichment for STAT5 binding and were associated with an opposing network of transcription factors, including PAX5, EBF1, PU.1, IRF4 and IKAROS. Patients with a high ratio of active STAT5 to NF-κB or IKAROS had more-aggressive disease. Our studies indicate that an imbalance of two opposing transcriptional programs drives B-ALL and suggest that restoring the balance of these pathways might inhibit B-ALL.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Katerndahl CDS,Heltemes-Harris LM,Willette MJL,Henzler CM,Frietze S,Yang R,Schjerven H,Silverstein KAT,Ramsey LB,Hubbard G,Wells AD,Kuiper RP,Scheijen B,van Leeuwen FN,Müschen M,Kornblau SM,Farrar MA

doi

10.1038/ni.3716

subject

Has Abstract

pub_date

2017-06-01 00:00:00

pages

694-704

issue

6

eissn

1529-2908

issn

1529-2916

pii

ni.3716

journal_volume

18

pub_type

杂志文章

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