Related Experiment Video
Updated: May 14, 2026
11:15
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Clinical implications of RAS mutations in AML: prognostic significance is based upon the involved gene and mutation
John N Colgan1,2,3, Jack H Peplinski4, Yi-Cheng Wang5
1Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA.
Blood Advances
|May 12, 2026
Summary
KRAS mutations, but not NRAS, worsen outcomes in acute myeloid leukemia (AML). Complex RAS mutations, especially in KMT2A-rearranged AML, indicate a poor prognosis for pediatric and young adult patients.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- Acute myeloid leukemia (AML) is a complex blood cancer with varied outcomes.
- NRAS and KRAS gene mutations are common in AML but their prognostic significance is unclear.
- KMT2A rearrangements are frequent in pediatric AML, necessitating investigation of RAS mutations within this subset.
Purpose of the Study:
- To evaluate the clinical impact of NRAS and KRAS mutations in a large cohort of pediatric and young adult AML patients.
- To specifically assess the role of RAS mutations in KMT2A-rearranged AML.
- To define and analyze the prognostic value of complex RAS mutations (Comp-RAS) in AML.
Main Methods:
- Analysis of next-generation sequencing (NGS) data from over 2000 pediatric and young adult AML patients.
- Identification and stratification of RAS (NRAS, KRAS) mutations and complex RAS mutations.
- Correlation of mutation status with clinical outcomes, including specific analysis in KMT2A-rearranged AML.
Main Results:
- RAS mutations were identified in 35.1% of patients (NRAS: 518, KRAS: 216).
- NRAS mutations showed no association with AML outcomes.
- KRAS mutations were linked to inferior outcomes in AML, particularly in KMT2A-rearranged AML.
- Complex RAS mutations (Comp-RAS) occurred in 13.5% of RAS-mutated patients and were associated with distinctly adverse outcomes.
Conclusions:
- KRAS mutations, unlike NRAS mutations, are associated with poor prognosis in AML.
- RAS mutation status, particularly complex KRAS mutations, significantly impacts outcomes in KMT2A-rearranged AML.
- Comp-RAS status is a key driver of adverse outcomes in the overall AML cohort, especially for KRAS-mutated patients.
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