Somatic mutations precede acute myeloid leukemia years before diagnosis
Pinkal Desai1, Nuria Mencia-Trinchant2, Oleksandr Savenkov3
1Division of Hematology and Oncology, Weill Cornell Medical College, New York, NY, USA. pid9006@med.cornell.edu.
Nature Medicine
|July 11, 2018
Summary
Mutations in genes like TP53, IDH1, and IDH2 can be detected years before acute myeloid leukemia (AML) diagnosis. Identifying these premalignant mutations may enable early detection and intervention strategies for AML.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- The somatic mutation patterns at acute myeloid leukemia (AML) diagnosis are known.
- The premalignant mutational landscape and its influence on AML risk and diagnosis timing remain unclear.
Purpose of the Study:
- To investigate the premalignant mutational landscape preceding acute myeloid leukemia (AML).
- To identify specific gene mutations associated with increased AML risk and delayed diagnosis.
Main Methods:
- Deep sequencing of peripheral blood DNA from 212 women who developed AML and age-matched controls.
- Analysis of mutations in IDH1, IDH2, TP53, DNMT3A, TET2, and spliceosome genes.
Main Results:
- Mutations in IDH1, IDH2, TP53, DNMT3A, TET2, and spliceosome genes were significantly associated with increased odds of developing AML.
- All patients with TP53 (21/21) and IDH1/IDH2 (15/15) mutations developed AML.
- Detectable mutations were found years prior to clinical AML diagnosis, indicating a latency period.
Conclusions:
- The presence of specific mutations years before diagnosis suggests a premalignant phase for AML.
- Early detection and monitoring during this latency period should be considered for intervention studies.
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