ReviewBlood2015
Secondary mutations as mediators of resistance to targeted therapy in leukemia.
Review in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 1 of them a synthesis that pooled it.
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
96 citing papers in PubMed, 1 synthesis or guideline pooled it, 153 citations in OpenAlex.
- FLT3 Tyrosine Kinase Inhibitors for the Treatment of Fit and Unfit Patients with FLT3-Mutated AML: A Systematic Review.International journal of molecular sciences · 2021Pooled it
- Randomized evaluation of quizartinib and low-dose ara-C vs low-dose ara-C in older acute myeloid leukemia patients.Blood advances · 2021Trial
- A phase I/II study of the combination of quizartinib with azacitidine or low-dose cytarabine for the treatment of patients with acute myeloid leukemia and myelodysplastic syndrome.Haematologica · 2021Trial
- Clinical resistance to crenolanib in acute myeloid leukemia due to diverse molecular mechanisms.Nature communications · 2019Trial
- Mislocalisation of FLT3-ITD receptor contributes to MV4-11 leukaemia cell resistance to antibody-drug conjugate.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- Treatment sequence with gilteritinib and allogeneic haematopoietic stem cell transplantation in relapsed/refractory FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukaemia patients: A multicentre real-world study.British journal of haematology · 2026Article
- Targeting FLT3 in Acute Myeloid Leukemia: Structural Insights and Key Challenges.ACS bio & med chem Au · 2026Review
- Article
- Overcoming MEN1-mediated resistance with menin inhibitor switching in KMT2A-rearranged acute myeloid leukemia.Leukemia · 2026Article
- Targeting epigenetic methylation: emerging diagnosis and therapeutic strategies in cancer.Experimental hematology & oncology · 2026Review
- Dynamic heterogeneity towards drug resistance in AML cells is primarily driven by epigenomic mechanism unveiled by multi-omics analysis.Journal of advanced research · 2026Article
- Review
- Current Therapeutic Strategies for FLT3-Mutated Acute Myeloid Leukemia: A Narrative Review.Cureus · 2025Review
- Counter-Therapeutic Strategies for Resistance of FLT3 Inhibitors in Acute Myeloid Leukemia.Cells · 2025Review
- Sitravatinib combined with venetoclax exerts effective synergy to eliminate acute myeloid leukemia cells with FLT3-ITD mutations.Translational oncology · 2025Article
- Concurrent inhibition of p300/CBP and FLT3 enhances cytotoxicity and overcomes resistance in acute myeloid leukemia.Acta pharmacologica Sinica · 2025Article
- Advances and Challenges in Quizartinib-Based FLT3 Inhibition for Acute Myeloid Leukemia: Mechanisms of Resistance and Prospective Combination Therapies.European journal of haematology · 2025Review
- Combined anti-leukemic effect of gilteritinib and GSK-J4 in FLT3-ITDTranslational oncology · 2025Article
- Advancements in Protein Kinase Inhibitors: From Discovery to Clinical Applications.Research (Washington, D.C.) · 2025Review
- Mitoxantrone-liposome SensitizesJournal of Cancer · 2025Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The advent of small molecule-based targeted therapy has improved the treatment of both acute and chronic leukemias. Resistance to small molecule inhibitors has emerged as a common theme. The most frequent mode of acquired resistance is the acquisition of point mutations in the kinase domain. FLT3 inhibitors have improved response rates in FLT3-mutated acute myeloid leukemia (AML). The occurrence of the ATP-binding site and activation loop mutations confers varying degrees of resistance to the individual FLT3 inhibitors. Second-generation FLT3 inhibitors such as crenolanib may overcome the resistance of these mutations. Furthermore, nonmutational mechanisms of resistance such as prosurvival pathways and bone marrow signaling may be upregulated in FLT3 inhibitor-resistant AML with secondary kinase domain mutations. More recently, point mutations conferring resistance to the Bruton tyrosine kinase inhibitor ibrutinib in chronic lymphocytic leukemia, arsenic trioxide in acute promyelocytic leukemia, and the BH3-mimetic ABT199 in lymphoma have been identified. In chronic myeloid leukemia, the emergence of tyrosine kinase domain mutations has historically been the dominant mechanism of resistance. The early identification of secondary point mutations and their downstream effects along with the development of second- or third-generation inhibitors and rationally designed small molecule combinations are potential strategies to overcome mutation-mediated resistance.
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.