Activated Intrinsic Apoptosis Pathway Is a Key Related Prognostic Parameter in Acute Myeloid Leukemia

Hess, Corine J.; Berkhof, Johannes; Denkers, Fedor; Ossenkoppele, Gert J.; Schouten, Jan P.; Oudejans, Joost J.; Waisfisz, Quinten; Schuurhuis, Gerrit Jan

doi:10.1200/jco.2006.08.4061

Cited by 45 publications

(35 citation statements)

References 18 publications

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“…This has been previously observed in an independent cohort of AML and chronic myeloid leukemia patients. 42,48 It is assumed that the increased expression of antiapoptotic genes, leading to oncogene addiction, is counterbalanced by elevated expression of proapoptotic genes, thus creating a "primed to cell death" status. 49 In our present study, we observed increased expression of TAK1 in a large panel of AML CD34…”

Section: Discussionmentioning

confidence: 99%

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The TAK1-NF-κB axis as therapeutic target for AML

Bosman

Schepers

Jaques

et al. 2014

Blood

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Section: Discussionmentioning

confidence: 99%

“…39 Overexpression of multiple antiapoptotic genes of the mitochondrial related BCL-2 family has been related to the development and/or maintenance of AML and is prognostically significant for the treatment outcome of this group of patients. [40][41][42][43][44][45][46][47] By comparing the apoptotic gene profile of AML CD34…”

Section: Discussionmentioning

confidence: 99%

The TAK1-NF-κB axis as therapeutic target for AML

Bosman

Schepers

Jaques

et al. 2014

Blood

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“…46 Gene expression profiling analyzing 31 apoptosis-related transcripts in newly diagnosed AML patients identified a threegene expression signature, including c-IAP2, to accurately predict poor overall survival. 49 Surprisingly, high expression of two pro-apoptotic genes, that is, BAX-(l) and BMF, also correlated with unfavorable survival besides c-IAP2. 49 This indicates that the prognostic impact of this gene signature may be due to an altered balance of pro-and anti-apoptotic genes.…”

mentioning

confidence: 99%

“…49 Surprisingly, high expression of two pro-apoptotic genes, that is, BAX-(l) and BMF, also correlated with unfavorable survival besides c-IAP2. 49 This indicates that the prognostic impact of this gene signature may be due to an altered balance of pro-and anti-apoptotic genes.…”

mentioning

confidence: 99%

Exploiting inhibitor of apoptosis proteins as therapeutic targets in hematological malignancies

Fulda

2012

Leukemia

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Resistance to apoptosis is one of the hallmarks of human cancers and contributes to the insensitivity of many cancers to commonly used treatment approaches. Inhibitor of apoptosis (IAP) proteins, a family of anti-apoptotic proteins, have an important role in evasion of apoptosis, as they can both block apoptosis-signaling pathways and promote survival. High expression of IAP proteins is observed in multiple cancers, including hematological malignancies, and has been associated with unfavorable prognosis and poor patients' outcome. Therefore, IAP proteins are currently considered as promising molecular targets for therapy. Indeed, drug-discovery approaches over the last decade aiming at neutralizing IAP proteins have resulted in the generation of small-molecule inhibitors or antisense oligonucleotides that demonstrated in vitro and in vivo antitumor activities in preclinical studies. As some of these strategies have already entered the stage of clinical evaluation, for example, in leukemia, an update on this promising molecular-targeted strategy to interfere with apoptotic pathways is of broad interest.

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“…2 On the contrary, studies assessing transcript levels of apoptosis signaling molecules showed inverse findings. 3 However, expression of single factors may not reflect the efficiency of the cell death machinery. For this reason we previously developed a different approach analyzing the functional integrity of apoptosis signaling in individual cells by simultaneously investigating 2 key apoptogenic events: mitochondrial release of cytochrome c and activation of caspase-3.…”

Section: Introductionmentioning

confidence: 99%

Intact apoptosis signaling in myeloid leukemia cells determines treatment outcome in childhood AML

Meyer

Queudeville

Eckhoff

et al. 2008

Blood

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Recently we reported that intact apoptosis signaling is indicative of favorable outcome in childhood acute lymphoblastic leukemia. Here we addressed this issue in 45 pediatric acute myeloid leukemia patients analyzing 2 core apoptogenic events: cytochrome c release and caspase-3 activation. In patients with good prognosis cytochrome c release was clearly found to be caspasedependent and correlated with activated caspase-3, indicating that activation of initiator or amplifier caspases such as caspase-8 together with an intact apoptosome function are elementary for favorable outcome. The functional integrity of this apoptogenic checkpoint is reflected by the parameter caspase-dependent cytochrome c-related activation of caspase-3 (CRAC(dep)). Patients with positive CRAC(dep) values (intact signaling) exhibited superior survival compared with CRAC(dep) negative patients (deficient signaling). Thus, the propensity to undergo apoptosis of leukemia cells is an important feature for favorable treatment outcome and may serve as an additional stratification tool for pediatric AML patients. This trial was registered at www.ClinicalTrials.gov as #NCT00111345.

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Activated Intrinsic Apoptosis Pathway Is a Key Related Prognostic Parameter in Acute Myeloid Leukemia

Cited by 45 publications

References 18 publications

The TAK1-NF-κB axis as therapeutic target for AML

The TAK1-NF-κB axis as therapeutic target for AML

Exploiting inhibitor of apoptosis proteins as therapeutic targets in hematological malignancies

Intact apoptosis signaling in myeloid leukemia cells determines treatment outcome in childhood AML

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