Blood Res.  2024;59:41. 10.1007/s44313-024-00044-4.

Acute myeloid leukemia and myelodysplastic neoplasms: clinical implications of myelodysplasia‑related genes mutations and TP53 aberrations

• Kim H
• Lee J
• Yu S
• Yoo E
• Kim H
• Lee S
• Lee W

• KMID: 2562543
• DOI: http://doi.org/10.1007/s44313-024-00044-4

Abstract

Purpose
The fifth World Health Organization (WHO) classification (2022 WHO) and International Consensus Classification (ICC) of myeloid neoplasms have recently been published. In this study, patients were reclassified according to the revised classification and their prognoses were analyzed to confirm the clinical utility of the new classifications.
Methods
We included 101 adult patients, 77 with acute myeloid leukemia (AML) and 24 with myelodysplastic neoplasms (MDS), who underwent bone marrow aspiration and next-generation sequencing (NGS) between August 2019 and July 2023. We reclassified the patients according to the revised criteria, examined the differences, and analyzed the prognosis using survival analysis.
Results
According to the 2022 WHO and ICC, 23 (29.9%) patients and 32 (41.6%) patients were reclassified into different groups, respectively, due to the addition of myelodysplasia-related (MR) gene mutations to the diagnostic criteria or the addition of new entities associated with TP53 mutations. The median overall survival (OS) of patients with AML and MR gene mutations was shorter than that of patients in other AML groups; however, the difference was not significant. Patients with AML and TP53 mutation had a significantly shorter OS than the other AML group (p = 0.0014, median OS 2.3 vs 10.3 months). They also had significantly shorter OS than the AML and MR mutation group (p = 0.002, median OS 2.3 vs 9.6 months).
Conclusion
The revised classifications allow for a more detailed categorization based on genetic abnormalities, which may be helpful in predicting prognosis. AML with TP53 mutations is a new ICC category that has shown a high prognostic significance in a small number of cases.

Keyword

Acute myeloid leukemia; Gene mutations; International Consensus Classification; World Health Organization

Figure

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  Fig. 1 Sankey diagram showing the reclassification of patients with (A) acute myeloid leukemia and (B) myelodysplastic neoplasm, from the 2016 World Health Organization (WHO) to the 2022 WHO and International Consensus Classification

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  Fig. 2 Molecular landscape of patients with acute myeloid leukemia

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  Fig. 3 Survival analysis of patients with acute myeloid leukemia (AML) and myelodysplasia-related (MR) gene mutations based on the 2022 WHO classification. (A) Survival outcomes between patients with AML and MR mutations and those with other types of AML. (B) Survival outcomes between groups of patients with AML with myelodysplastic changes (MRC), classified according to the 2016 WHO and MR gene mutation criteria in the 2022 WHO, and those with AML, not otherwise specified, according to the 2016 WHO and AML with MR gene mutation in the 2022 WHO. (C) Survival outcomes between groups of patients with AML with MRC based on the 2016 WHO and AML with MR gene mutations in the 2022 WHO, and those with AML with MRC in the 2016 WHO but without MR gene mutation in the 2022 WHO. (D) Survival outcomes between groups of patients of AML with MR gene mutations and cytogenetic abnormalities

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  Fig. 4 Survival analysis of patients with AML and TP53 mutations based on the international consensus classification. A Survival outcomes between patients in AML with TP53 mutations and other AML group. B Survival outcomes between patients in AML with TP53 mutation and AML with myelodysplasia-related gene mutations

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