Dataset Information

Reclassification of Acute Myeloid Leukemia According to the 2016 WHO Classification.

ABSTRACT: We reviewed our leukemia database to reclassify 610 patients previously diagnosed as having acute myeloid leukemia (AML) according to the updated 2016 WHO classification. Nine patients were categorized as having myelodysplastic syndrome and myeloid neoplasms with germline predisposition. AML with recurrent genetic abnormalities accounted for 57.4% (345/601) of the patients under the 2016 WHO classification. AML with mutated NPM1 was the most common form (16.5%), with the majority associated with monocytic differentiation (63.6%). AML with double CEBPA mutations accounted for 8.3% of these cases, and the majority were previously diagnosed as AML with/without maturation (78.0%). These newly classified mutations were mutually exclusive without overlapping with other forms of AML with recurrent genetic abnormalities. AML with mutated NPM1 and AML with myelodysplasia-related changes comprised the oldest patients, whereas AML with RUNX1-RUNX1T1 included the youngest patients. The leukocyte count was highest in AML with mutated NPM1, and the percentage of peripheral blood blasts was the highest in AML with double CEBPA mutations. Our results indicate that implementation of the 2016 WHO classification of AML would not pose major difficulties in clinical practice. Hematopathologists should review and prepare genetic tests for the new classification, according to their clinical laboratory conditions.

SUBMITTER: Jung J

PROVIDER: S-EPMC6340847 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Reclassification of Acute Myeloid Leukemia According to the 2016 WHO Classification.

Jung Jin J Cho Byung Sik BS Kim Hee Je HJ Han Eunhee E Jang Woori W Han Kyungja K Lee Jae Wook JW Chung Nack Gyun NG Cho Bin B Kim Myungshin M Kim Yonggoo Y

Annals of laboratory medicine 20190501 3

We reviewed our leukemia database to reclassify 610 patients previously diagnosed as having acute myeloid leukemia (AML) according to the updated 2016 WHO classification. Nine patients were categorized as having myelodysplastic syndrome and myeloid neoplasms with germline predisposition. AML with recurrent genetic abnormalities accounted for 57.4% (345/601) of the patients under the 2016 WHO classification. AML with mutated <i>NPM1</i> was the most common form (16.5%), with the majority associat ...[more]

PMID: 30623623

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Project description:BackgroundRecent studies have provided a detailed census of genes that are mutated in acute myeloid leukemia (AML). Our next challenge is to understand how this genetic diversity defines the pathophysiology of AML and informs clinical practice.MethodsWe enrolled a total of 1540 patients in three prospective trials of intensive therapy. Combining driver mutations in 111 cancer genes with cytogenetic and clinical data, we defined AML genomic subgroups and their relevance to clinical outcomes.ResultsWe identified 5234 driver mutations across 76 genes or genomic regions, with 2 or more drivers identified in 86% of the patients. Patterns of co-mutation compartmentalized the cohort into 11 classes, each with distinct diagnostic features and clinical outcomes. In addition to currently defined AML subgroups, three heterogeneous genomic categories emerged: AML with mutations in genes encoding chromatin, RNA-splicing regulators, or both (in 18% of patients); AML with TP53 mutations, chromosomal aneuploidies, or both (in 13%); and, provisionally, AML with IDH2(R172) mutations (in 1%). Patients with chromatin-spliceosome and TP53-aneuploidy AML had poor outcomes, with the various class-defining mutations contributing independently and additively to the outcome. In addition to class-defining lesions, other co-occurring driver mutations also had a substantial effect on overall survival. The prognostic effects of individual mutations were often significantly altered by the presence or absence of other driver mutations. Such gene-gene interactions were especially pronounced for NPM1-mutated AML, in which patterns of co-mutation identified groups with a favorable or adverse prognosis. These predictions require validation in prospective clinical trials.ConclusionsThe driver landscape in AML reveals distinct molecular subgroups that reflect discrete paths in the evolution of AML, informing disease classification and prognostic stratification. (Funded by the Wellcome Trust and others; ClinicalTrials.gov number, NCT00146120.).

Dataset Information

Reclassification of Acute Myeloid Leukemia According to the 2016 WHO Classification.

Publications

Reclassification of Acute Myeloid Leukemia According to the 2016 WHO Classification.

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