ArticleBlood2011
An antiapoptotic BCL-2 family expression index predicts the response of chronic lymphocytic leukemia to ABT-737.
Article in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
58 citing papers in PubMed, 84 citations in OpenAlex.
- A phase 2 study of the BH3 mimetic BCL2 inhibitor navitoclax (ABT-263) with or without rituximab, in previously untreated B-cell chronic lymphocytic leukemia.Leukemia & lymphoma · 2015Trial
- An overview of prognostic markers in patients with CLL.Frontiers in oncology · 2024Review
- NOD2 silencing promotes cell apoptosis and inhibits drug resistance in chronic lymphocytic leukemia by inhibiting the NF-κB signaling pathway.Journal of biochemical and molecular toxicology · 2023Article
- Bcl-B: an "unknown" protein of the Bcl-2 family.Biology direct · 2023Review
- Targeting BCL2 pathways in CLL: a story of resistance and ingenuity.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- Extrinsic interactions in the microenvironment in vivo activate an antiapoptotic multidrug-resistant phenotype in CLL.Blood advances · 2021Article
- Novel Agents in Chronic Lymphocytic Leukemia: New Combination Therapies and Strategies to Overcome Resistance.Cancers · 2021Review
- Targeting BCL-2 in B-cell malignancies and overcoming therapeutic resistance.Cell death & disease · 2020Review
- N-locking stabilization of covalent helical peptides: Application to Bfl-1 antagonists.Chemical biology & drug design · 2020Article
- Article
- Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins.Nature reviews. Molecular cell biology · 2019Review
- Repression of Mcl-1 expression by the CDC7/CDK9 inhibitor PHA-767491 overcomes bone marrow stroma-mediated drug resistance in AML.Scientific reports · 2018Article
- Antiapoptotic BCL-2 proteins determine sorafenib/regorafenib resistance and BH3-mimetic efficacy in hepatocellular carcinoma.Oncotarget · 2018Article
- Systems modeling accurately predicts responses to genotoxic agents and their synergism with BCL-2 inhibitors in triple negative breast cancer cells.Cell death & disease · 2018Article
- Targeting the Bcl-2 Family in B Cell Lymphoma.Frontiers in oncology · 2018Review
- Article
- CK2 and PI3K are direct molecular targets of quercetin in chronic lymphocytic leukaemia.Oncotarget · 2017Article
- MLL-AF4 binds directly to a BCL-2 specific enhancer and modulates H3K27 acetylation.Experimental hematology · 2017Article
- Gene expression profiling of tumor-initiating stem cells from mouse Krebs-2 carcinoma using a novel marker of poorly differentiated cells.Oncotarget · 2017Article
- BCL-W has a fundamental role in B cell survival and lymphomagenesis.The Journal of clinical investigation · 2017Article
Corrections and comments
- Commented on by
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
The antiapoptotic BCL-2 proteins regulate lymphocyte survival and are over-expressed in lymphoid malignancies, including chronic lymphocytic leukemia. The small molecule inhibitor ABT-737 binds with high affinity to BCL-2, BCL-XL, and BCL-W but with low affinity to MCL-1, BFL-1, and BCL-B. The active analog of ABT-737, navitoclax, has shown a high therapeutic index in lymphoid malignancies; developing a predictive marker for it would be clinically valuable for patient selection or choice of drug combinations. Here we used RT-PCR as a highly sensitive and quantitative assay to compare expression of antiapoptotic BCL-2 genes that are known to be targeted by ABT-737. Our findings reveal that the relative ratio of MCL-1 and BFL-1 to BCL-2 expression provides a highly significant linear correlation with ABT-737 sensitivity (r = 0.6, P < .001). In contrast, antiapoptotic transcript levels, used individually or in combination for high or low affinity ABT-737-binding proteins, could not predict ABT-737 sensitivity. The (MCL-1 + BFL-1)/BCL-2 ratio was validated in a panel of leukemic cell lines subjected to genetic and pharmacologic manipulations. Changes after ABT-737 treatment included increased expression of BFL-1 and BCL-B that may contribute to treatment resistance. This study defines a highly significant BCL-2 expression index for predicting the response of CLL to ABT-737.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.