NF-κB and FLIP in arsenic trioxide (ATO)-induced apoptosis in myelodysplastic syndromes (MDSs)

Kerbauy, Daniella; Lesnikov, Vladimir; Abbasi, Nissa; Seal, Sudeshna; Scott, Bart L.; Deeg, H. Joachim

doi:10.1182/blood-2005-04-1424

Cited by 85 publications

(94 citation statements)

References 53 publications

(72 reference statements)

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“…Two studies performed on a limited number of patients did not reach a consensus on the status of intrinsic NF-B activity in MDS. 63,64 Two recent studies performed on 24 65 and 55 MDS 10 patients clearly revealed that the degree of NF-kB activation correlated with the risk of progression to AML, both in transversal and in longitudinal studies.…”

Section: Myelodysplastic Syndromesmentioning

confidence: 99%

“…65 This assumption was based on the correlation between the relative expression level of two TNF-a R subunits (R1 or p55 versus R2 or p75) and the degree of NF-kB activation in MDS. In patients where R1 predominated over R2, NF-kB activation was maximal.…”

Section: Myelodysplastic Syndromesmentioning

confidence: 99%

“…In patients where R1 predominated over R2, NF-kB activation was maximal. 65 This can be correlated with fundamental studies suggesting that TNF-a R1 (p55) preferentially induces caspase-dependent apoptosis via the extrinsic TNF receptor-associated protein with a death domain (TRADD)/Fas-associated death domain protein (FADD)/caspase-8/caspase-3 pathway (which would be incompatible with NF-kB activation), 66 while TNF-a R2 (p75) would activate NF-kB. 65 Thus, this study insinuates that NF-kB activation involve a paracrine (and hence non-cell autonomous) contribution and also suggests that changes in TNF-a R1/R2 expression might be involved in disease progression.…”

Section: Myelodysplastic Syndromesmentioning

confidence: 99%

“…To reconcile these two distinct theories explaining NF-kB activation in MDS (cell autonomous 10 and TNF-a-driven 65 ), one might invoke two distinct possibilities. Either, cytogenetic alterations (and secondary mutations?)…”

Section: Myelodysplastic Syndromesmentioning

confidence: 99%

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Targeting NF-κB in hematologic malignancies

et al. 2006

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The transcription factor nuclear factor kappa B (NF-jB) can intervene in oncogenesis by virtue of its capacity to regulate the expression of a plethora of genes that modulate apoptosis, and cell survival as well as proliferation, inflammation, tumor metastasis and angiogenesis. Different reports demonstrate the intrinsic activation of NF-jB in lymphoid and myeloid malignancies, including preneoplastic conditions such as myelodysplastic syndromes, underscoring its implication in malignant transformation. Targeting intrinsic NF-jB activation, as well as its upstream and downstream regulators, may hence constitute an additional approach to the oncologist's armamentarium. Several small inhibitors of the NF-jB-activatory kinase IjB kinase, of the proteaseome, or of the DNA binding of NF-jB subunits are under intensive investigation. Currently used cytotoxic agents can induce NF-jB activation as an unwarranted side effect, which confers apoptosis suppression and hence resistance to these drugs. Thus, NF-jB inhibitory molecules may be clinically useful, either as single therapeutic agents or in combination with classical chemotherapeutic agents, for the treatment of hematological malignancies.

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Section: Myelodysplastic Syndromesmentioning

confidence: 99%

Section: Myelodysplastic Syndromesmentioning

confidence: 99%

Section: Myelodysplastic Syndromesmentioning

confidence: 99%

Section: Myelodysplastic Syndromesmentioning

confidence: 99%

See 2 more Smart Citations

Targeting NF-κB in hematologic malignancies

et al. 2006

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“…The expression of several of the proteins that negatively regulate apoptosis depends on the transcriptional activity of nuclear factor (NF)-kB. It is now established that NF-kB can be constitutively activated as cells progress from low-to high-grade myelodysplasia and acute myeloid leukemia, suggesting that inhibitors of the NF-kB pathway may be interesting to test to reverse the disease progression (Braun et al, 2006;Kerbauy et al, 2005).…”

Section: Mitochondria Caspases and Hematopoietic Cell Differentiationmentioning

confidence: 99%