Unknown

Dataset Information

0

Ebf1 or Pax5 haploinsufficiency synergizes with STAT5 activation to initiate acute lymphoblastic leukemia.


ABSTRACT: As STAT5 is critical for the differentiation, proliferation, and survival of progenitor B cells, this transcription factor may play a role in acute lymphoblastic leukemia (ALL). Here, we show increased expression of activated signal transducer and activator of transcription 5 (STAT5), which is correlated with poor prognosis, in ALL patient cells. Mutations in EBF1 and PAX5, genes critical for B cell development have also been identified in human ALL. To determine whether mutations in Ebf1 or Pax5 synergize with STAT5 activation to induce ALL, we crossed mice expressing a constitutively active form of STAT5 (Stat5b-CA) with mice heterozygous for Ebf1 or Pax5. Haploinsufficiency of either Pax5 or Ebf1 synergized with Stat5b-CA to rapidly induce ALL in 100% of the mice. The leukemic cells displayed reduced expression of both Pax5 and Ebf1, but this had little effect on most EBF1 or PAX5 target genes. Only a subset of target genes was deregulated; this subset included a large percentage of potential tumor suppressor genes and oncogenes. Further, most of these genes appear to be jointly regulated by both EBF1 and PAX5. Our findings suggest a model whereby small perturbations in a self-reinforcing network of transcription factors critical for B cell development, specifically PAX5 and EBF1, cooperate with STAT5 activation to initiate ALL.

SUBMITTER: Heltemes-Harris LM 

PROVIDER: S-EPMC3173246 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

Ebf1 or Pax5 haploinsufficiency synergizes with STAT5 activation to initiate acute lymphoblastic leukemia.

Heltemes-Harris Lynn M LM   Willette Mark J L MJ   Ramsey Laura B LB   Qiu Yi Hua YH   Neeley E Shannon ES   Zhang Nianxiang N   Thomas Deborah A DA   Koeuth Thearith T   Baechler Emily C EC   Kornblau Steven M SM   Farrar Michael A MA  

The Journal of experimental medicine 20110523 6


As STAT5 is critical for the differentiation, proliferation, and survival of progenitor B cells, this transcription factor may play a role in acute lymphoblastic leukemia (ALL). Here, we show increased expression of activated signal transducer and activator of transcription 5 (STAT5), which is correlated with poor prognosis, in ALL patient cells. Mutations in EBF1 and PAX5, genes critical for B cell development have also been identified in human ALL. To determine whether mutations in Ebf1 or Pax  ...[more]

Similar Datasets

2011-05-09 | E-GEOD-25645 | biostudies-arrayexpress
2011-05-09 | GSE25645 | GEO
2021-11-02 | PXD017147 | Pride
| S-EPMC6525306 | biostudies-literature
| S-EPMC8671594 | biostudies-literature
| S-EPMC7100125 | biostudies-literature
| S-EPMC6187160 | biostudies-literature
| S-EPMC7540392 | biostudies-literature
| S-EPMC3369288 | biostudies-literature
| S-EPMC9750140 | biostudies-literature