Among patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with a complex karyotype (CK), TP53 mutations are linked with more aggressive disease, according to research published in Blood Advances.

CK is defined as the presence of at least 3 chromosomal abnormalities in patients with cancer. Up to 12% of patients with AML, and 30% of patients with MDS, have CK. The presence of 3 and 4 abnormalities are linked with poor and very poor cytogenetic risk, respectively, per Revised International Prognostic Scoring System criteria.

TP53 mutations are common in both MDS and AML with a CK, though such mutations are relatively uncommon in de novo AML. For this study, researchers evaluated whether CK with a TP53 mutation represented a biologically homogenous group of MDS and AML cases.

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Overall, data from 299 patients were included, of whom 144 and 155 had AML and MDS, respectively. One hundred and eighteen and 81 patients, furthermore, had therapy-related and de novo disease, respectively.

Analysis of patient samples showed that mutations were present in 96% of individuals in the overall cohort. The most common mutation was, furthermore, TP53, which was noted in 83% of patients, and was more common among patients with therapy-related disease (P =.008). Patients with CK with a TP53 mutation had lower hemoglobin levels (P =.004) and trended towards presentation at an older age (P =.06) than did those without a TP53 mutation.

The presence of TP53 mutations was, furthermore, linked with worse clinical outcomes (P =.0017). Multihit TP53 mutation was the strongest predictor of a poor outcome of analyzed variables.

“Our data…confirm the importance of multihit status of the TP53 mutation in driving prognosis in this combined AML and MDS cohort,” the authors wrote in their report. “Future studies to validate this observation in cohorts that incorporate TP53 loss-of-heterozygosity status as well as prospective studies on TP53 CK patients are warranted to better understand the biology underlying their highly aggressive behavior.”


Weinberg OK, Siddon A, Madanat YF, et al. TP53 mutation defines a unique subgroup within complex karyotype de novo and therapy-related MDS/AML. Blood Adv. 2022;6(9):2847-2853. doi:10.1182/bloodadvances.2021006239