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. 2024 Feb 1;109(2):671-675.
doi: 10.3324/haematol.2023.283510.

Exclusion of persistent mutations in splicing factor genes and isocitrate dehydrogenase 2 improves the prognostic power of molecular measurable residual disease assessment in acute myeloid leukemia

Tracy Murphy  1 , Jinfeng Zou  1 , Andrea Arruda  1 , Ting Ting Wang  1 , Zhen Zhao  1 , Yangqiao Zheng  1 , Vikas Gupta  1 , Dawn Maze  1 , Caroline McNamara  2 , Mark D Minden  1 , Aaron Schimmer  1 , Hassan Sibai  1 , Karen Yee  1 , Jose-Mario Capo-Chichi  3 , Tracy Stockley  3 , Andre Schuh  1 , Scott V Bratman  1 , Steven M Chan  4
Affiliations

Exclusion of persistent mutations in splicing factor genes and isocitrate dehydrogenase 2 improves the prognostic power of molecular measurable residual disease assessment in acute myeloid leukemia

Tracy Murphy et al. Haematologica. .
No abstract available

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Figures

Figure 1.
Figure 1.
Evaluation of the impact of exclusion or inclusion of myeloid malignancy-associated mutations on the prognostic power of molecular measurable residual disease assessment. (A) Heatmap showing each of the 2,500 unique permutations ordered according to their associated hazard ratios for overall survival. A yellow cell indicates exclusion of the indicated gene mutation for measurable residual disease assessment, whereas a blue cell indicates inclusion. (B) Volcano plot showing statistical significance plotted against the D statistic from the Kolmogorov-Smirnov test comparing the distribution of hazard ratios of permutations in which the indicated gene mutation is excluded versus the reference distribution. See text for details. (C) Violin plots showing the distribution of hazard ratios of permutations in which the indicated gene mutation is included (+) for measurable residual disease assessment. HR: hazard ratio.
Figure 2.
Figure 2.
Exclusion of mutations in splicing factor genes and IDH2 in addition to DNMT3A, TET2, and ASXL1 mutations improves the prognostic power of molecular measurable residual disease assess ment. Kaplan-Meier plots for (A) overall survival (OS), (B) relapse-free survival (RFS), and (C) cumulative incidence of relapse (CIR) of patients classified as measurable residual disease (MRD)-positive (MRD+) or MRD-negative (MRD-) and based on whether DNMT3A, TET2, and ASXL1 (DTA) mutations or mutations in DTA, splicing factor genes and IDH2 (DTAS12) were excluded from MRD determination. A mutant allele frequency of >0.01 (1%) at timepoints 1 and 2 was used to define MRD positivity. Comparison of the hazard ratios for OS, RFS, and CIR in the Morita et al. (D) or Ahn et al. (E) validation cohort between exclusion of mutations in DTA alone versus DTAS12 for determination of MRD status. A mutant allele frequency of >0.01 (1%) was used to define MRD positivity. The hazard ratios and P values shown in all panels were calculated using the Cox proportional-hazards model.
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References

    1. Dohner H, Wei AH, Appelbaum FR, et al. . Diagnosis and management of AML in adults: 2022 ELN recommendations from an international expert panel. Blood. 2022;129(4):424-447. - PMC - PubMed
    1. Walter RB, Ofran Y, Wierzbowska A, et al. . Measurable residual disease as a biomarker in acute myeloid leukemia: theoretical and practical considerations. Leukemia. 2021;35(6):1529-1538. - PubMed
    1. Jongen-Lavrencic M, Grob T, Hanekamp D, et al. . Molecular minimal residual disease in acute myeloid leukemia. N Engl J Med. 2018;378(13):1189-1199. - PubMed
    1. Morita K, Kantarjian HM, Wang F, et al. . Clearance of somatic mutations at remission and the risk of relapse in acute myeloid leukemia. J Clin Oncol. 2018;36(18):1788-1797. - PMC - PubMed
    1. Tanaka T, Morita K, Loghavi S, et al. . Clonal dynamics and clinical implications of postremission clonal hematopoiesis in acute myeloid leukemia. Blood. 2021;138(18):1733-1739. - PMC - PubMed

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