ArticleBlood advances2020
Fusion partner-specific mutation profiles and KRAS mutations as adverse prognostic factors in MLL-rearranged AML.
Article in Blood advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Characteristics and Prognostic Implications in Newly Diagnosed KMT2Ar AML: A Multicenter Study of the ECLA Group.American journal of hematology · 2026Article
- Clinical implications of RAS mutations in AML: prognostic significance is based upon the involved gene and mutation complexity.Blood advances · 2026Article
- Genomic Profiling, Induction Response, and Transplant Outcomes in Pediatric Acute Myeloid Leukemia: A Single-Center Retrospective Cohort Study.International journal of molecular sciences · 2026Article
- Age-specific mutation profiles and their prognostic implications in pediatricHaematologica · 2026Article
- Review
- Outcomes of acute myeloid leukemia with KMT2A (MLL) rearrangement: a multicenter study of TROPHY group.Blood cancer journal · 2025Article
- Establishment of a high-risk pediatric AML-derived cell line YCU-AML2 with genetic and metabolic vulnerabilities.International journal of hematology · 2025Article
- Rearrangements involving 11q23.3/KMT2A in adult AML: mutational landscape and prognostic implications - a HARMONY study.Leukemia · 2024Article
- KRAS G12 mutations as adverse prognostic factors in KMT2A-rearranged acute myeloid leukemia.Leukemia · 2024Article
- Monoallelic KRAS (G13C) mutation triggers dysregulated expansion in induced pluripotent stem cell-derived hematopoietic progenitor cells.Stem cell research & therapy · 2024Article
- Identification of prognostic and driver gene mutations in acute myeloid leukemia by a bioinformatics analysis.Translational cancer research · 2023Article
- Advances in molecular characterization of pediatric acute megakaryoblastic leukemia not associated with Down syndrome; impact on therapy development.Frontiers in cell and developmental biology · 2023Review
- Article
- [The efficacy and safety of CLAG-M/I regimen for relapsed or refractory acute myeloid leukemia in children].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2022Article
- Article
- Impact of KMT2A Rearrangement and CSPG4 Expression in Pediatric Acute Myeloid Leukemia.Cancers · 2021Article
- Review
- CLAG-M chemotherapy followed by umbilical cord blood stem cell transplantation for primary refractory acute myeloid leukaemia in a child: A case report.World journal of clinical cases · 2020Article
- Concomitant Pathogenic Mutations and Fusions of Driver Oncogenes in Tumors.Frontiers in oncology · 2020Review
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Authors and funding
24 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mixed-lineage leukemia (MLL) gene rearrangements are among the most frequent chromosomal abnormalities in acute myeloid leukemia (AML). MLL fusion patterns are associated with the patient's prognosis; however, their relationship with driver mutations is unclear. We conducted sequence analyses of 338 genes in pediatric patients with MLL-rearranged (MLL-r) AML (n = 56; JPLSG AML-05 study) alongside data from the TARGET study's pediatric cohorts with MLL-r AML (n = 104), non-MLL-r AML (n = 581), and adult MLL-r AML (n = 81). KRAS mutations were most frequent in pediatric patients with high-risk MLL fusions (MLL-MLLLT10, MLL-MLLT4, and MLL-MLLT1). Pediatric patients with MLL-r AML (n = 160) and a KRAS mutation (KRAS-MT) had a significantly worse prognosis than those without a KRAS mutation (KRAS-WT) (5-year event-free survival [EFS]: 51.8% vs 18.3%, P < .0001; 5-year overall survival [OS]: 67.3% vs 44.3%, P = .003). The adverse prognostic impact of KRAS mutations was confirmed in adult MLL-r AML. KRAS mutations were associated with adverse prognoses in pediatric patients with both high-risk (MLLT10+MLLT4+MLLT1; n = 60) and intermediate-to-low-risk (MLLT3+ELL+others; n = 100) MLL fusions. The prognosis did not differ significantly between patients with non-MLL-r AML with KRAS-WT or KRAS-MT. Multivariate analysis showed the presence of a KRAS mutation to be an independent prognostic factor for EFS (hazard ratio [HR], 2.21; 95% confidence interval [CI], 1.35-3.59; P = .002) and OS (HR, 1.85; 95% CI, 1.01-3.31; P = .045) in MLL-r AML. The mutation is a distinct adverse prognostic factor in MLL-r AML, regardless of risk subgroup, and is potentially useful for accurate treatment stratification. This trial was registered at the UMIN (University Hospital Medical Information Network) Clinical Trials Registry (UMIN-CTR; http://www.umin.ac.jp/ctr/index.htm) as #UMIN000000511.
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