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. 2022 Dec 29;15(1):198.
doi: 10.3390/cancers15010198.

The Impact of Mutation of Myelodysplasia-Related Genes in De Novo Acute Myeloid Leukemia Carrying NPM1 Mutation

Yi Wang  1   2 , Andres E Quesada  2 , Zhuang Zuo  2 , L Jeffrey Medeiros  2 , C Cameron Yin  2 , Shaoying Li  2 , Jie Xu  2 , Gautam Borthakur  3 , Yisheng Li  4 , Chao Yang  4 , Yasmin Abaza  5 , Juehua Gao  6 , Xinyan Lu  6 , M James You  2 , Yizhuo Zhang  1   7   8 , Pei Lin  2
Affiliations

The Impact of Mutation of Myelodysplasia-Related Genes in De Novo Acute Myeloid Leukemia Carrying NPM1 Mutation

Yi Wang et al. Cancers (Basel). .

Abstract

Background: The impact of gene mutations typically associated with myelodysplastic syndrome (MDS) in acute myeloid leukemia (AML) with NPM1 mutation is unclear. Methods: Using a cohort of 107 patients with NPM1-mutated AML treated with risk-adapted therapy, we compared survival outcomes of patients without MDS-related gene mutations (group A) with those carrying concurrent FLT3-ITD (group B) or with MDS-related gene mutations (group C). Minimal measurable disease (MMD) status assessed by multiparameter flow cytometry (MFC), polymerase chain reaction (PCR), and/or next-generation sequencing (NGS) were reviewed. Results: Among the 69 patients treated intensively, group C showed significantly inferior progression-free survival (PFS, p < 0.0001) but not overall survival (OS, p = 0.055) compared to group A. Though groups A and C had a similar MMD rate, group C patients had a higher relapse rate (p = 0.016). Relapse correlated with MMD status at the end of cycle 2 induction (p = 0.023). Survival of group C patients was similar to that of group B. Conclusion: MDS-related gene mutations are associated with an inferior survival in NPM1-mutated AML.

Keywords: AML; MMD; NPM1.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Mutational landscape of 107 cases of NPM1 mutated AML. Mutations of genes acquired at relapse are highlighted in orange and those at diagnosis in blue. Each column represents a patient.
Figure 2
Figure 2
Correlation of MMD status at EOC1 and EOC2 with relapse. MMD, minimal measurable disease; EOC1, end of cycle 1 induction; EOC2, end of cycle 2 induction.
Figure 3
Figure 3
Kaplan–Meier curves comparing groups A and C show significant difference in PFS (a) but not OS (b). Kaplan–Meier curves comparing groups B and C show no significant difference in PFS (c) or OS (d). Group A, without MDS-related gene mutations; Group B, with FLT3-ITD; Group C, with MDS-related gene mutations.
See this image and copyright information in PMC

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