AML With Genetic Abnormalities Other Than Translocations
AML With Genetic Abnormalities Other Than Translocations
Since the introduction of the 2008 WHO classification and ELN system of AML risk stratification, new recurrent genetic aberrations in AML have been discovered. This session of the workshop focused on cases of CN-AML and illustrated the morphologic spectrum and molecular genetic features of AML cases with NPM1, FLT3-ITD, DNMT3A, CEBPA, and other common AML-associated mutations. De novo CN-AML with the NPM1 mutation is best classified according to the mutation rather than as AML-MRC, despite morphologic evidence of dysplasia or additional chromosomal aberrations such as trisomy 4, 8, or 21. An early phase of de novo AML should be suspected, especially in younger patients, when a short latency period is noted and blast percentage is in the range of CMML. In the setting of AML relapse, dominance of expanded subclones or new clones may alter the risk group, usually manifested as low-risk subgroup (NPM1 mutation only), moving up to a higher risk subgroup (NPM1 and FLT3-ITD). Currently, screening for NPM1, CEPBA, FLT3-ITD, and DNMT3 mutations is recommended in routine clinical practice. Quantitative PCR for mutant NPM1 is an excellent marker for monitoring MRD. As deep sequencing becomes more affordable and available, more genes of clinical significance can be screened. The future of AML classification is likely to be based on a more comprehensive molecular characterization of neoplastic clones and subclones for better risk stratification and targeted therapy.
Summary
Since the introduction of the 2008 WHO classification and ELN system of AML risk stratification, new recurrent genetic aberrations in AML have been discovered. This session of the workshop focused on cases of CN-AML and illustrated the morphologic spectrum and molecular genetic features of AML cases with NPM1, FLT3-ITD, DNMT3A, CEBPA, and other common AML-associated mutations. De novo CN-AML with the NPM1 mutation is best classified according to the mutation rather than as AML-MRC, despite morphologic evidence of dysplasia or additional chromosomal aberrations such as trisomy 4, 8, or 21. An early phase of de novo AML should be suspected, especially in younger patients, when a short latency period is noted and blast percentage is in the range of CMML. In the setting of AML relapse, dominance of expanded subclones or new clones may alter the risk group, usually manifested as low-risk subgroup (NPM1 mutation only), moving up to a higher risk subgroup (NPM1 and FLT3-ITD). Currently, screening for NPM1, CEPBA, FLT3-ITD, and DNMT3 mutations is recommended in routine clinical practice. Quantitative PCR for mutant NPM1 is an excellent marker for monitoring MRD. As deep sequencing becomes more affordable and available, more genes of clinical significance can be screened. The future of AML classification is likely to be based on a more comprehensive molecular characterization of neoplastic clones and subclones for better risk stratification and targeted therapy.
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