# NPM1 and IDH1/2 Mutations Show Limited Prognostic Impact in Relapsed/Refractory AML: Evidence From the AVALON Cohort **Authors:** Calogero Vetro, Irene Azzali, Elisabetta Petracci, Cristina Papayannidis, Eleonora Eleuteri, Fanny Erika Palumbo, Vincenzo Federico, Nicola Fracchiolla, Patrizia Zappasodi, Maria Paola Martelli, Maria Benedetta Giannini, Lorenzo Brunetti, Raffaele Palmieri, Jacopo Nanni, Giorgia Simonetti, Fabio Guolo, Paola Minetto, Luca Maurillo, Federica Gigli, Atto Billio, Elisabetta Todisco, Giovanni Martinelli, Giovanni Marconi PMC · DOI: 10.1002/hon.70169 · 2026-01-13 ## TL;DR In a study of relapsed/refractory AML patients treated with venetoclax and hypomethylating agents, NPM1 and IDH1/2 mutations did not affect treatment response or survival. ## Contribution The study shows that NPM1 and IDH1/2 mutations have limited prognostic value in relapsed/refractory AML under this treatment. ## Key findings - NPM1 and IDH1/2 mutations did not significantly affect response rates in the AVALON cohort. - Survival outcomes were not influenced by the presence of NPM1 or IDH1/2 mutations in treated patients. ## Abstract In the AVALON cohort of relapsed/refractory AML treated with venetoclax plus hypomethylating agents, NPM1 and IDH1/2 mutations showed no significant impact on response or survival. These findings indicate that prognostic models for relapsed AML should consider treatment context rather than baseline mutation status. ## Linked entities - **Genes:** NPM1 (nucleophosmin 1) [NCBI Gene 4869], IDH1 (isocitrate dehydrogenase (NADP(+)) 1) [NCBI Gene 3417], IDH2 (isocitrate dehydrogenase (NADP(+)) 2) [NCBI Gene 3418] - **Chemicals:** venetoclax (PubChem CID 49846579) - **Diseases:** AML (MONDO:0018874) ## Full-text entities - **Genes:** FLT3 (fms related receptor tyrosine kinase 3) [NCBI Gene 2322] {aka CD135, FLK-2, FLK2, STK1}, SF3B1 (splicing factor 3b subunit 1) [NCBI Gene 23451] {aka Hsh155, MDS, PRP10, PRPF10, SAP155, SF3b155}, PGR (progesterone receptor) [NCBI Gene 5241] {aka NR3C3, PR}, IDH1 (isocitrate dehydrogenase (NADP(+)) 1) [NCBI Gene 3417] {aka HEL-216, HEL-S-26, IDCD, IDH, IDP, IDPC}, NPM1 (nucleophosmin 1) [NCBI Gene 4869] {aka B23, NPM}, ELN (elastin) [NCBI Gene 2006] {aka ADCL1, SVAS, WBS, WS}, NF1 (neurofibromin 1) [NCBI Gene 4763] {aka NFNS, VRNF, WSS}, CEBPA (CCAAT enhancer binding protein alpha) [NCBI Gene 1050] {aka C/EBP-alpha, CEBP}, PTPN11 (protein tyrosine phosphatase non-receptor type 11) [NCBI Gene 5781] {aka BPTP3, CFC, JMML, METCDS, NS1, PTP-1D}, ASXL1 (ASXL transcriptional regulator 1) [NCBI Gene 171023] {aka BOPS, MDS}, DDX41 (DEAD-box helicase 41) [NCBI Gene 51428] {aka ABS, MPLPF}, NRAS (NRAS proto-oncogene, GTPase) [NCBI Gene 4893] {aka ALPS4, CMNS, N-ras, NCMS, NRAS1, NS6}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, KRAS (KRAS proto-oncogene, GTPase) [NCBI Gene 3845] {aka 'C-K-RAS, C-K-RAS, CFC2, K-RAS2A, K-RAS2B, K-RAS4A}, IDH2 (isocitrate dehydrogenase (NADP(+)) 2) [NCBI Gene 3418] {aka D2HGA2, ICD-M, IDH, IDH-2, IDHM, IDP} - **Diseases:** extramedullary disease (MESH:D023981), glioma (MESH:D005910), ND (MESH:D065886), AML (MESH:D015470), death (MESH:D003643), tumorigenesis (MESH:D063646) - **Chemicals:** HMA (-), VEN (MESH:C579720) - **Species:** Homo sapiens (human, species) [taxon 9606] ## Figures 1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12797279/full.md --- Source: https://tomesphere.com/paper/PMC12797279