PMID- 20130599
OWN - NLM
STAT- MEDLINE
DCOM- 20100520
LR  - 20211020
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 24
IP  - 4
DP  - 2010 Apr
TI  - NF-kappaB activation mediates resistance to IFN beta in MLL-rearranged acute 
      lymphoblastic leukemia.
PG  - 806-12
LID - 10.1038/leu.2010.2 [doi]
AB  - Acute lymphoblastic leukemia (ALL) harboring the t(4;11) translocation is 
      associated with a very poor prognosis; innovative treatment strategies are 
      required to improve the current 5-year survival rate of 30-40%. Interferon beta 
      (IFN beta) has shown promise in the treatment of both solid and hematologic 
      malignancies, although the short half-life and toxicity associated with high 
      doses have limited its clinical utility. To overcome these limitations, we 
      investigated the effect of continuous, gene transfer-mediated delivery of IFN 
      beta using adeno-associated virus (AAV)-mediated expression, on ALL cells with 
      the t(4;11) translocation. We found that this method of IFN beta delivery 
      resulted in complete remission of leukemia in a murine model. However, leukemic 
      cells eventually became resistant to IFN beta and relapse was observed. 
      Activation of NF-kappaB was identified as a mechanism for IFN beta resistance, 
      and inhibition of NF-kappaB activity in resistant cells sensitized cells to IFN 
      beta. IFN beta combined with agents that inhibit NF-kappaB could have therapeutic 
      potential in the treatment of children with mixed lineage leukemia subtype ALL.
FAU - Tracey, L
AU  - Tracey L
AD  - Department of Surgery, St Jude Children's Research Hospital, Memphis, TN 38105, 
      USA.
FAU - Streck, C J
AU  - Streck CJ
FAU - Du, Z
AU  - Du Z
FAU - Williams, R F
AU  - Williams RF
FAU - Pfeffer, L M
AU  - Pfeffer LM
FAU - Nathwani, A C
AU  - Nathwani AC
FAU - Davidoff, A M
AU  - Davidoff AM
LA  - eng
GR  - R01 CA133322/CA/NCI NIH HHS/United States
GR  - CA21766/CA/NCI NIH HHS/United States
GR  - R01CA1333222-01A1/CA/NCI NIH HHS/United States
GR  - R01 CA133322-02/CA/NCI NIH HHS/United States
GR  - R01 CA133322-01A1/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100204
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 149025-06-9 (Myeloid-Lymphoid Leukemia Protein)
RN  - 77238-31-4 (Interferon-beta)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/genetics/metabolism
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/drug effects
MH  - Blotting, Western
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Chromosomes, Human, Pair 11/genetics
MH  - Chromosomes, Human, Pair 4/genetics
MH  - Dependovirus/genetics
MH  - Drug Resistance, Neoplasm
MH  - Electrophoretic Mobility Shift Assay
MH  - Flow Cytometry
MH  - *Gene Expression Regulation, Leukemic
MH  - *Gene Rearrangement
MH  - Humans
MH  - Interferon-beta/*pharmacology
MH  - JNK Mitogen-Activated Protein Kinases/genetics/metabolism
MH  - Male
MH  - Mice
MH  - Mice, SCID
MH  - Myeloid-Lymphoid Leukemia Protein/*genetics/metabolism
MH  - NF-kappa B/genetics/*metabolism
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy/genetics/*metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Translocation, Genetic
MH  - Tumor Cells, Cultured
MH  - Xenograft Model Antitumor Assays
PMC - PMC4657731
MID - NIHMS262254
EDAT- 2010/02/05 06:00
MHDA- 2010/05/21 06:00
PMCR- 2015/11/24
CRDT- 2010/02/05 06:00
PHST- 2010/02/05 06:00 [entrez]
PHST- 2010/02/05 06:00 [pubmed]
PHST- 2010/05/21 06:00 [medline]
PHST- 2015/11/24 00:00 [pmc-release]
AID - leu20102 [pii]
AID - 10.1038/leu.2010.2 [doi]
PST - ppublish
SO  - Leukemia. 2010 Apr;24(4):806-12. doi: 10.1038/leu.2010.2. Epub 2010 Feb 4.