Trial reportBlood2015
BRAF inhibitors reverse the unique molecular signature and phenotype of hairy cell leukemia and exert potent antileukemic activity.
Trial report in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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
42 citing papers in PubMed, 96 citations in OpenAlex.
- Long-term results of the sequential combination of cladribine and rituximab in Hairy cell leukemia.Leukemia & lymphoma · 2024Trial
- Targeting Mutant BRAF in Relapsed or Refractory Hairy-Cell Leukemia.The New England journal of medicine · 2015Trial
- Small Molecule Therapeutic Approaches With a Greater Focus on Hearing Loss: A Review.Health science reports · 2026Article
- DUSP1 is a key driver of disease persistence and potential therapeutic target in hairy cell leukemia.Blood advances · 2026Article
- Hairy cell leukemia: a chronic B-cell lymphoma with unique clinicopathological features and unresolved molecular mechanisms.Blood advances · 2026Review
- Hairy Cell Leukemia With Splenic Rupture: Hematological Changes and Disappearance of Hairy Morphology After Splenectomy.Journal of hematology · 2025Article
- Immune activation and microenvironmental crosstalk in hairy cell leukemia.Frontiers in immunology · 2025Review
- Non-canonicalOncology research · 2024Review
- BRAF(V600E) mutation together with loss of Trp53 or pTEN drives the origination of hairy cell leukemia from B-lymphocytes.Molecular cancer · 2023Article
- The protective role of the microenvironment in hairy cell leukemia treatment: Facts and perspectives.Frontiers in oncology · 2023Review
- Development of a distributed international patient data registry for hairy cell leukemia.Leukemia & lymphoma · 2022Article
- Hairy Cell Leukemia (HCL) and HCL Variant: Updates and Spotlights on Therapeutic Advances.Current oncology reports · 2022Review
- Application of precision medicine in clinical routine in haematology-Challenges and opportunities.Journal of internal medicine · 2022Review
- Hairy cell leukemia: a specific 17-gene expression signature points to new targets for therapy.Journal of cancer research and clinical oncology · 2022Article
- Article
- Treatment of Classic Hairy Cell Leukemia: Targeting Minimal Residual Disease beyond Cladribine.Cancers · 2022Review
- Review
- KRAS and RAS-MAPK Pathway Deregulation in Mature B Cell Lymphoproliferative Disorders.Cancers · 2022Review
- Novel targeted treatments in hairy cell leukemia and other hairy cell-like disorders.Frontiers in oncology · 2022Review
- Updates in hairy cell leukemia (HCL) and variant-type HCL (HCL-V): rationale for targeted treatments with a focus on ibrutinib.Therapeutic advances in hematology · 2022Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 3 countries.
Funding
Abstract
Hairy cell leukemia (HCL) shows unique clinicopathological and biological features. HCL responds well to purine analogs but relapses are frequent and novel therapies are required. BRAF-V600E is the key driver mutation in HCL and distinguishes it from other B-cell lymphomas, including HCL-like leukemias/lymphomas (HCL-variant and splenic marginal zone lymphoma). The kinase-activating BRAF-V600E mutation also represents an ideal therapeutic target in HCL. Here, we investigated the biological and therapeutic importance of the activated BRAF-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) pathway in HCL by exposing in vitro primary leukemic cells purified from 26 patients to clinically available BRAF (vemurafenib; dabrafenib) or MEK (trametinib) inhibitors. Results were validated in vivo in samples from vemurafenib-treated HCL patients within a phase 2 clinical trial. BRAF and MEK inhibitors caused, specifically in HCL (but not HCL-like) cells, marked MEK/ERK dephosphorylation, silencing of the BRAF-MEK-ERK pathway transcriptional output, loss of the HCL-specific gene expression signature, downregulation of the HCL markers CD25, tartrate-resistant acid phosphatase, and cyclin D1, smoothening of leukemic cells' hairy surface, and, eventually, apoptosis. Apoptosis was partially blunted by coculture with bone marrow stromal cells antagonizing MEK-ERK dephosphorylation. This protective effect could be counteracted by combined BRAF and MEK inhibition. Our results strongly support and inform the clinical use of BRAF and MEK inhibitors in HCL.
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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.