Interpretative differences of combined cytogenetic and molecular profiling highlights differences between MRC and ELN classifications of AML.

TitleInterpretative differences of combined cytogenetic and molecular profiling highlights differences between MRC and ELN classifications of AML.
Publication TypeJournal Article
Year of Publication2021
AuthorsSussman RT, Manning B, Ackerman D, Bigdeli A, Pammer P, Velu PD, Luger SM, Bagg A, Carroll M, Morrissette JJD
JournalCancer Genet
Date Published2021 08
KeywordsCell Line, Tumor, Chromosome Aberrations, Cohort Studies, Cytogenetic Analysis, Gamma Rays, Gene Expression Profiling, Humans, Leukemia, Myeloid, Acute, Mutation, Risk Assessment, Risk Factors, Tumor Suppressor Protein p53

Acute myeloid leukemia (AML) is typically characterized clinically for prognostic purposes using both cytogenetic and molecular characteristics. However, both cytogenetic and molecular risk stratification schemas are varied and few reports have studied correlations between these schemas. We have performed a single institution retrospective review of cytogenetic and molecular classifications of AMLs seen at Penn Medicine between 2013 and 2018. One-hundred fourty-four cases were characterized according to European Leukemia Net (ELN) or Medical Research Council (MRC) criteria for cytogenetics and results compared to molecular profiling. When we analyzed the most common sequencing study results within the risk groupings, negative sequencing studies and FLT3 mutations were common in favorable AMLs, intermediate AMLs had mutations in FLT3, NPM1, DNMT3A and IDH2, while adverse AMLs had a high prevalence of TP53 mutations. We next grouped the genes on the panel by their proteins' functions and found mutations in signaling pathway genes to be common in favorable AMLs while tumor suppressors were commonly mutated in adverse AMLs. AMLs grouped by the type of chromosomal abnormality present showed that FLT3 mutations were common in AMLs with a trisomy while TP53 mutations were common in AMLs with a monosomy or a deletion. TP53 mutations are especially common in AMLs with a monosomal karyotype and often overlap with 17p loss. Interestingly, although all AMLs with TP53 mutations have a defect in the response to DNA damage, expression of P53 protein before and after irradiation is not consistently predicted by phenotype. Overall, these studies confirm the genetic complexity of AML which does not fall into simple patterns of cooperating mutations.

Alternate JournalCancer Genet
PubMed ID33915454
Related Faculty: 
Priya Velu, M.D., Ph.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700