Format

Send to

Choose Destination
See comment in PubMed Commons below
Leuk Lymphoma. 2004 Jun;45(6):1181-4.

Constitutive NF-kappab/Rel activation in philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL).

Author information

1
Abteilung Innere Medizin III, Universit├Ąt Ulm, Germany. Gerd.Munzert@bc.boehringer-ingelheim.com

Abstract

The Bcr-Abl translocation t(9;22)(q34;q11 ) defines a subgroup of ALL patients with a dismal prognosis despite the introduction of intensified induction and consolidation regimen. Although Bcr-Abl induced NF-kappaB/Rel activation has previously been shown, the role of NF-kappaB/Rel in Ph+ leukemia is unclear. Using DNA binding assays, we demonstrate constitutive NF-kappaB/Rel activity in nuclear extracts from Ph+ ALL blasts, whereas Ph- primary blast cells and B-precursor cell lines lack NF-kappaB/Rel activity. NF-kappaB/Rel activity was shown in the ela2 and the b2a2 subtypes. Constitutive NF-kappaB/Rel activity in Ph+ blasts is not due to elevated endogenous IkappaB kinase (IKK) activity as shown by immune complex kinase assays. Since NF-kappaB/Rel is a transcriptional regulator of inhibitors of apoptosis we examined the expression of anti-apoptotic genes known to be induced by NF-kappaB/Rel by real time PCR analysis. We found no induction of TRAFI, TRAF2, cIAPI, cIAP2, XIAP, A20 or Bfl/Al in Ph+ ALL samples as compared to Ph-negative ALL controls. In summary, constitutive NF-kappaB/Rel activation independent of endogenous IKK activation may be a common finding in Ph+ ALL. However, targets of NF-kappaB/Rel mediated transcriptional regulation in this disease remain to be identified.

PMID:
15359998
[Indexed for MEDLINE]

Publication types, MeSH terms, Substances

Publication types

MeSH terms

Substances

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Loading ...
    Support Center