Trial reportLeukemia2006
Relapse of acute promyelocytic leukemia with PML-RARalpha mutant subclones independent of proximate all-trans retinoic acid selection pressure.
Trial report in Leukemia, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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
12 citing papers in PubMed, 27 citations in OpenAlex.
- All-trans retinoic acid and late relapses in acute promyelocytic leukemia: very long-term follow-up of the North American Intergroup Study I0129.Leukemia research · 2013Trial
- A relapsed/refractory acute promyelocytic leukemia achieving complete response after chemotherapy with venetoclax.Medicine · 2025Article
- Function of PML-RARA in Acute Promyelocytic Leukemia.Advances in experimental medicine and biology · 2024Review
- Dual impacts of mesenchymal stem cell-derived exosomes on cancer cells: unravelling complex interactions.Journal of cell communication and signaling · 2023Review
- Relapsed/refractory acute promyelocytic leukemia with RARA-LBD region mutation was salvaged by venetoclax: A case report.Medicine · 2021Article
- Acute myeloid leukemia maturation lineage influences residual disease and relapse following differentiation therapy.Nature communications · 2021Article
- Article
- Retinoic acid receptor alpha drives cell cycle progression and is associated with increased sensitivity to retinoids in T-cell lymphoma.Oncotarget · 2017Article
- Article
- Valproic acid induces differentiation and transient tumor regression, but spares leukemia-initiating activity in mouse models of APL.Leukemia · 2012Article
- PML-RARalpha ligand-binding domain deletion mutations associated with reduced disease control and outcome after first relapse of APL.Leukemia · 2010Article
- Topoisomerase IIbeta negatively modulates retinoic acid receptor alpha function: a novel mechanism of retinoic acid resistance.Molecular and cellular biology · 2008Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Relapse of acute promyelocytic leukemia (APL) following all-trans retinoic acid (ATRA) therapy has been associated with the acquisition of mutations in the high-affinity ATRA binding site in PML-RARalpha, but little information is available about the selection dynamics of the mutation-harboring subclones. In this study, 6/18 patients treated with sequential ATRA and chemotherapy on protocol INT0129 relapsed with complete replacement of the nonmutant pretreatment APL cell population by a PML-RARalpha mutant subclone. Two patients relapsed in proximity of ATRA treatment; however, in four patients there was a 6-48 month hiatus between the last ATRA treatment and relapse. The mutant subclones were not detectable in samples tested > or = 3 months before relapse at > or = 1 in 10(2) (10(-2)) sensitivity. In one patient, a functionally weak mutation was detected at 10(-4) sensitivity before therapy but only limited pre-relapse enrichment of the mutant subclone was observed on subsequent ATRA therapy. These results indicate that proximate ATRA selection pressure is frequently not the main determinant for the emergence of strongly dominant PML-RARalpha mutant subclones and suggest that APL subclones harboring PML-RARalpha mutations are predisposed to the acquisition of secondary genetic/epigenetic alterations that result in a growth/survival advantage.
Indexed as
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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.