![Characterization of AML cases with durable remission. (A) Genomic landscape of AML cases with durable remission. Molecular profile for 18 patients with ongoing remission for >12 months (date cutoff, 28 February 2019). The presence of adverse cytogenetic risk, complex karyotype, del(17p), indicated mutations, study ID number, relapse-free survival (in months), and cytotoxic therapy received (AZA, azacitidine; DEC, decitabine; or LDAC) are shown for each case. The bar graphs (right side of the plot) summarize the number of cases with persistent mutations or reduced/cleared mutations or where MRD was not assessed in remission. (B) Quantitative MRD profile of NPM1 mutation in 4 AML cases as assessed by RT-qPCR. MRD levels are expressed as percent relative to baseline transcript level. Positive detection is shown as solid-filled black circles, whereas negative detection is shown as open circles, indicating the assay sensitivity relative to amplification of the ABL gene. (C) Quantitative MRD profile of IDH2 mutation in 7 AML cases as assessed by Droplet Digital PCR (n = 5) and next-generation sequencing (NGS) panel (n = 2, both had high VAF). One additional case (#044) tested negative in remission by Sanger sequencing only and is not included in this figure. Morphologic relapse is indicated by an “R”. Undetectable IDH2mut level is indicated by “Neg”. (D) Kaplan-Meier plots of OS of patients with NPM1 or IDH2 mutant AML treated with venetoclax in combination with either DNMTi or LDAC compared with patients WT for both NPM1 and IDH2. Four patients had concurrent NPM1 and IDH2 mutations and were included twice. One patient was excluded due to unknown molecular status. (E) Kaplan-Meier plots of OS of patients with IDH1 mutant AML treated with venetoclax in combination with either DNMTi or LDAC compared with patients WT for IDH1. One patient was excluded due to unknown molecular status. (F) Volcano plot of differential gene expression associated with NPM1 mutation in responders: NPM1mut (n = 4) vs NPM1 WT (n = 6). No genes were significantly differentially expressed (DE) with FDR <5%. HOX genes are highlighted in green and apoptosis pathway genes in purple. Gene set enrichment analysis confirmed activation of the NPM1mut signature (using correlation adjusted mean rank gene set analysis [CAMERA], top 3 NPM1mut gene sets, FDR range from 5.17 × 10−21 to 2.51 × 10−27). (G) Volcano plot of differential gene expression associated with NPM1 mutation in TCGA dataset: NPM1mut (n = 35) vs NPM1 WT (n = 115). Gene sets are colored as in panel F, with differentially expressed genes in blue and red. Gene set enrichment analysis confirmed activation of the NPM1mut signature (using CAMERA, top 3 NPM1mut gene sets, FDR range 1.9 × 10−34 to 1.1 × 10−37).](https://ash.silverchair-cdn.com/ash/content_public/journal/blood/135/11/10.1182_blood.2019003988/5/bloodbld2019003988f2.png?Expires=1735498253&Signature=bCEsU2Kr2ljgOCSiYrJH3grYbQTdr5jlShaB4hy6Ga9UMIshwN0~NBRz875ESNMNomh2IWrH-HgwRBIQLF4mAc4464tzg22AroAoVaUHTmq5aADWt~PDbY35qhe~aNacROzw-AP~YAImQ~cQNaO8DxCh7F4HJszrisnsGjeO~gC3lkIetuJKtMDc2S3CcBAmkZjczNFS6d~9Uo2NiKmIW4X-7Jne8WzZaI9jJxhLQ6gWlMrbqCmv86hFI3fDUSJ6u2bPNVSlLmKz~QOwlZz8NJuoYjAN4WM7KzLRjOYdR0KR0y1YPoJUB6WSYKHvXiK8KpKmUv5BqOO7UgWGRaSfqQ__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
Characterization of AML cases with durable remission. (A) Genomic landscape of AML cases with durable remission. Molecular profile for 18 patients with ongoing remission for >12 months (date cutoff, 28 February 2019). The presence of adverse cytogenetic risk, complex karyotype, del(17p), indicated mutations, study ID number, relapse-free survival (in months), and cytotoxic therapy received (AZA, azacitidine; DEC, decitabine; or LDAC) are shown for each case. The bar graphs (right side of the plot) summarize the number of cases with persistent mutations or reduced/cleared mutations or where MRD was not assessed in remission. (B) Quantitative MRD profile of NPM1 mutation in 4 AML cases as assessed by RT-qPCR. MRD levels are expressed as percent relative to baseline transcript level. Positive detection is shown as solid-filled black circles, whereas negative detection is shown as open circles, indicating the assay sensitivity relative to amplification of the ABL gene. (C) Quantitative MRD profile of IDH2 mutation in 7 AML cases as assessed by Droplet Digital PCR (n = 5) and next-generation sequencing (NGS) panel (n = 2, both had high VAF). One additional case (#044) tested negative in remission by Sanger sequencing only and is not included in this figure. Morphologic relapse is indicated by an “R”. Undetectable IDH2mut level is indicated by “Neg”. (D) Kaplan-Meier plots of OS of patients with NPM1 or IDH2 mutant AML treated with venetoclax in combination with either DNMTi or LDAC compared with patients WT for both NPM1 and IDH2. Four patients had concurrent NPM1 and IDH2 mutations and were included twice. One patient was excluded due to unknown molecular status. (E) Kaplan-Meier plots of OS of patients with IDH1 mutant AML treated with venetoclax in combination with either DNMTi or LDAC compared with patients WT for IDH1. One patient was excluded due to unknown molecular status. (F) Volcano plot of differential gene expression associated with NPM1 mutation in responders: NPM1mut (n = 4) vs NPM1 WT (n = 6). No genes were significantly differentially expressed (DE) with FDR <5%. HOX genes are highlighted in green and apoptosis pathway genes in purple. Gene set enrichment analysis confirmed activation of the NPM1mut signature (using correlation adjusted mean rank gene set analysis [CAMERA], top 3 NPM1mut gene sets, FDR range from 5.17 × 10−21 to 2.51 × 10−27). (G) Volcano plot of differential gene expression associated with NPM1 mutation in TCGA dataset: NPM1mut (n = 35) vs NPM1 WT (n = 115). Gene sets are colored as in panel F, with differentially expressed genes in blue and red. Gene set enrichment analysis confirmed activation of the NPM1mut signature (using CAMERA, top 3 NPM1mut gene sets, FDR range 1.9 × 10−34 to 1.1 × 10−37).