Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Molecular measurable residual disease monitoring and transplant indications in NPM1 mutated acute myeloid leukemia

Bone Marrow Transplantation volume 60, pages 135–143 (2025)Cite this article

Subjects

Abstract

NPM1 mutated acute myeloid leukemia (AML) comprises roughly 30% of all AML cases and is mainly classified as favorable or intermediate-risk according to the European Leukemia Net stratification. Some patients, however, either have a poor response to initial intensive chemotherapy or ultimately relapse. NPM1 mutations are common, generally stable at early relapse and AML specific, features which make them ideal targets for measurable residual disease (MRD) monitoring. MRD monitoring via molecular analysis during the course of treatment can inform the role of allogeneic stem cell transplantation (HCT) in first remission in patients with NPM1 mutated AML with high-risk co-occurring mutations, particularly FLT3-ITD, and in favorable risk patients who do not achieve defined molecular milestones. In this review, we evaluate the prognostic role of MRD monitoring in NPM1 mutated AML and its use as a predictive biomarker to refine risk stratification and inform decision making regarding treatment. We explore the impact of pre-HCT MRD positivity on post-HCT outcomes in this AML subset, and how HCT-related factors such as conditioning intensity may influence this risk.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Co-mutation characteristics of NPM1 mutated AML.
Fig. 2

Similar content being viewed by others

References

  1. Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016;374:2209–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Sasaki K, Ravandi F, Kadia TM, DiNardo CD, Short NJ, Borthakur G, et al. De novo acute myeloid leukemia: a population-based study of outcome in the United States based on the surveillance, epidemiology, and end results (SEER) database, 1980 to 2017. Cancer. 2021;127:2049–61.

    Article  PubMed  Google Scholar 

  3. Shlush LI, Zandi S, Mitchell A, Chen WC, Brandwein JM, Gupta V, et al. Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia. Nature. 2014;506:328–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Falini B, Martelli MP, Bolli N, Sportoletti P, Liso A, Tiacci E, et al. Acute myeloid leukemia with mutated nucleophosmin (NPM1): is it a distinct entity? Blood. 2011;117:1109–20.

    Article  CAS  PubMed  Google Scholar 

  5. Schlenk Richard F, Döhner K, Krauter J, Fröhling S, Corbacioglu A, Bullinger L, et al. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. New Eng J Med. 2008;358:1909–18.

  6. Döhner H, Wei AH, Appelbaum FR, Craddock C, DiNardo CD, Dombret H, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022;140:1345–77.

    Article  PubMed  Google Scholar 

  7. Becker H, Marcucci G, Maharry K, Radmacher MD, Mrózek K, Margeson D, et al. Favorable prognostic impact of NPM1 mutations in older patients with cytogenetically normal de novo acute myeloid leukemia and associated gene- and microRNA-expression signatures: a cancer and leukemia group B study. J Clin Oncol. 2010;28:596–604.

    Article  CAS  PubMed  Google Scholar 

  8. Metzeler KH, Herold T, Rothenberg-Thurley M, Amler S, Sauerland MC, Görlich D, et al. Spectrum and prognostic relevance of driver gene mutations in acute myeloid leukemia. Blood. 2016;128:686–98.

    Article  CAS  PubMed  Google Scholar 

  9. Khoury JD, Solary E, Abla O, Akkari Y, Alaggio R, Apperley JF, et al. The 5th edition of the World Health Organization classification of haematolymphoid tumours: myeloid and histiocytic/dendritic neoplasms. Leukemia. 2022;36:1703–19.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Arber DA, Orazi A, Hasserjian RP, Borowitz MJ, Calvo KR, Kvasnicka HM, et al. International consensus classification of myeloid neoplasms and acute leukemias: integrating morphologic, clinical, and genomic data. Blood. 2022;140:1200–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Balsat M, Renneville A, Thomas X, de Botton S, Caillot D, Marceau A, et al. Postinduction minimal residual disease predicts outcome and benefit from allogeneic stem cell transplantation in acute myeloid leukemia with NPM1 mutation: a study by the acute leukemia French association group. J Clin Oncol. 2017;35:185–93.

    Article  CAS  PubMed  Google Scholar 

  12. Poiré X, Labopin M, Polge E, Blaise D, Chevallier P, Maertens J, et al. Hematopoietic stem cell transplantation for adult patients with isolated NPM1 mutated acute myeloid leukemia in first remission. Am J Hematol. 2019;94:231–9.

    Article  PubMed  Google Scholar 

  13. Borrow J, Dyer SA, Akiki S, Griffiths MJ. Molecular roulette: nucleophosmin mutations in AML are orchestrated through N-nucleotide addition by TdT. Blood. 2019;134:2291–303.

    Article  CAS  PubMed  Google Scholar 

  14. Falini B, Bolli N, Shan J, Martelli MP, Liso A, Pucciarini A, et al. Both carboxy-terminus NES motif and mutated tryptophan(s) are crucial for aberrant nuclear export of nucleophosmin leukemic mutants in NPMc+ AML. Blood. 2006;107:4514–23.

    Article  CAS  PubMed  Google Scholar 

  15. Falini B, Mecucci C, Tiacci E, Alcalay M, Rosati R, Pasqualucci L, et al. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med. 2005;352:254–66.

    Article  CAS  PubMed  Google Scholar 

  16. Vassiliou GS, Cooper JL, Rad R, Li J, Rice S, Uren A, et al. Mutant nucleophosmin and cooperating pathways drive leukemia initiation and progression in mice. Nat Genet. 2011;43:470–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Bolli N, Nicoletti I, De Marco MF, Bigerna B, Pucciarini A, Mannucci R, et al. Born to be exported: COOH-terminal nuclear export signals of different strength ensure cytoplasmic accumulation of nucleophosmin leukemic mutants. Cancer Res. 2007;67:6230–7.

    Article  CAS  PubMed  Google Scholar 

  18. Corces-Zimmerman MR, Hong WJ, Weissman IL, Medeiros BC, Majeti R. Preleukemic mutations in human acute myeloid leukemia affect epigenetic regulators and persist in remission. Proc Natl Acad Sci USA. 2014;111:2548–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Abelson S, Collord G, Ng SWK, Weissbrod O, Mendelson Cohen N, Niemeyer E, et al. Prediction of acute myeloid leukaemia risk in healthy individuals. Nature. 2018;559:400–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Loberg MA, Bell RK, Goodwin LO, Eudy E, Miles LA, SanMiguel JM, et al. Sequentially inducible mouse models reveal that NPM1 mutation causes malignant transformation of dnmt3a-mutant clonal hematopoiesis. Leukemia. 2019;33:1635–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Herudkova Z, Culen M, Folta A, Jeziskova I, Cerna J, Loja T, et al. Clonal hierarchy of main molecular lesions in acute myeloid leukaemia. Br J Haematol. 2020;190:562–72.

    Article  CAS  PubMed  Google Scholar 

  22. Potter N, Miraki-Moud F, Ermini L, Titley I, Vijayaraghavan G, Papaemmanuil E, et al. Single cell analysis of clonal architecture in acute myeloid leukaemia. Leukemia. 2019;33:1113–23.

    Article  CAS  PubMed  Google Scholar 

  23. Hubmann M, Köhnke T, Hoster E, Schneider S, Dufour A, Zellmeier E, et al. Molecular response assessment by quantitative real-time polymerase chain reaction after induction therapy in NPM1-mutated patients identifies those at high risk of relapse. Haematologica. 2014;99:1317–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Krönke J, Bullinger L, Teleanu V, Tschürtz F, Gaidzik VI, Kühn MW, et al. Clonal evolution in relapsed NPM1-mutated acute myeloid leukemia. Blood. 2013;122:100–8.

    Article  PubMed  Google Scholar 

  25. Garciaz S, Hospital MA, Saillard C, Hicheri Y, D’Incan E, Rey J, et al. IDH mutations identify a subgroup of NPM1 patients with a more favorable prognosis. a retrospective multicenter study of the filo group. Blood. 2020;136:39–40.

    Article  Google Scholar 

  26. Paschka P, Schlenk RF, Gaidzik VI, Habdank M, Krönke J, Bullinger L, et al. IDH1 and IDH2 mutations are frequent genetic alterations in acute myeloid leukemia and confer adverse prognosis in cytogenetically normal acute myeloid leukemia with NPM1 mutation without FLT3 internal tandem duplication. J Clin Oncol. 2010;28:3636–43.

    Article  CAS  PubMed  Google Scholar 

  27. Ley Timothy J, Ding L, Walter Matthew J, McLellan Michael D, Lamprecht T, Larson David E, et al. DNMT3A mutations in acute myeloid leukemia. New Eng J Med. 2010;363:2424–33.

  28. Chou W-C, Chou S-C, Liu C-Y, Chen C-Y, Hou H-A, Kuo Y-Y, et al. TET2 mutation is an unfavorable prognostic factor in acute myeloid leukemia patients with intermediate-risk cytogenetics. Blood. 2011;118:3803–10.

    Article  CAS  PubMed  Google Scholar 

  29. Döhner K, Schlenk RF, Habdank M, Scholl C, Rücker FG, Corbacioglu A, et al. Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics: interaction with other gene mutations. Blood. 2005;106:3740–6.

    Article  PubMed  Google Scholar 

  30. Boddu P, Kantarjian H, Borthakur G, Kadia T, Daver N, Pierce S, et al. Co-occurrence of FLT3-TKD and NPM1 mutations defines a highly favorable prognostic AML group. Blood Adv. 2017;1:1546–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Liu J, Qin W, Wang B, Wang Z, Hua H, Zhou F, et al. PTPN11 mutations in adult acute myeloid leukaemia: Prevalence and clinical implications in the context of NPM1 mutation. Leuk Res. 2022;118:106859.

    Article  CAS  PubMed  Google Scholar 

  32. El Hussein S, DiNardo CD, Takahashi K, Khoury JD, Fang H, Furudate K, et al. Acquired WT1 mutations contribute to relapse of NPM1-mutated acute myeloid leukemia following allogeneic hematopoietic stem cell transplant. Bone Marrow Transplant. 2022;57:370–6.

    Article  CAS  PubMed  Google Scholar 

  33. Kayser S, Benner A, Thiede C, Martens U, Huber J, Stadtherr P, et al. Pretransplant NPM1 MRD levels predict outcome after allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia. Blood Cancer J. 2016;6:e449.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Ivey A, Hills RK, Simpson MA, Jovanovic JV, Gilkes A, Grech A, et al. Assessment of minimal residual disease in standard-risk AML. N Engl J Med. 2016;374:422–33.

    Article  CAS  PubMed  Google Scholar 

  35. Heuser M, Freeman SD, Ossenkoppele GJ, Buccisano F, Hourigan CS, Ngai LL, et al. 2021 update on MRD in acute myeloid leukemia: a consensus document from the European LeukemiaNet MRD Working Party. Blood. 2021;138:2753–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Short NJ, Fu C, Berry DA, Walter RB, Freeman SD, Hourigan CS, et al. Association of hematologic response and assay sensitivity on the prognostic impact of measurable residual disease in acute myeloid leukemia: a systematic review and meta-analysis. Leukemia. 2022;36:2817–26.

    Article  PubMed  Google Scholar 

  37. Hourigan CS, Dillon LW, Gui G, Logan BR, Fei M, Ghannam J, et al. Impact of conditioning intensity of allogeneic transplantation for acute myeloid leukemia with genomic evidence of residual disease. J Clin Oncol. 2020;38:1273–83.

    Article  CAS  PubMed  Google Scholar 

  38. Pratz KW, Jonas BA, Pullarkat V, Recher C, Schuh AC, Thirman MJ, et al. Measurable residual disease response and prognosis in treatment-naïve acute myeloid leukemia with venetoclax and azacitidine. J Clin Oncol. 2021;40:855–65.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Krönke J, Schlenk RF, Jensen KO, Tschürtz F, Corbacioglu A, Gaidzik VI, et al. Monitoring of minimal residual disease in NPM1-mutated acute myeloid leukemia: a study from the German-Austrian acute myeloid leukemia study group. J Clin Oncol. 2011;29:2709–16.

    Article  PubMed  Google Scholar 

  40. Kapp-Schwoerer S, Weber D, Corbacioglu A, Gaidzik VI, Paschka P, Krönke J, et al. Impact of gemtuzumab ozogamicin on MRD and relapse risk in patients with NPM1-mutated AML: results from the AMLSG 09-09 trial. Blood. 2020;136:3041–50.

    Article  CAS  PubMed  Google Scholar 

  41. Jongen-Lavrencic M, Grob T, Hanekamp D, Kavelaars François G, al Hinai A, Zeilemaker A, et al. Molecular minimal residual disease in acute myeloid leukemia. N Engl J Med. 2018;378:1189–99.

    Article  CAS  PubMed  Google Scholar 

  42. Othman J, Tiong IS, O’Nions J, Dennis M, Mokretar K, Ivey A, et al. Molecular MRD is strongly prognostic in patients with NPM1-mutated AML receiving venetoclax-based nonintensive therapy. Blood. 2024;143:336–41.

    Article  CAS  PubMed  Google Scholar 

  43. Pettersson L, Johansson Alm S, Almstedt A, Chen Y, Orrsjö G, Shah-Barkhordar G, et al. Comparison of RNA- and DNA-based methods for measurable residual disease analysis in NPM1-mutated acute myeloid leukemia. Int J Lab Hematol. 2021;43:664–74.

    Article  PubMed  Google Scholar 

  44. Salipante SJ, Fromm JR, Shendure J, Wood BL, Wu D. Detection of minimal residual disease in NPM1-mutated acute myeloid leukemia by next-generation sequencing. Mod Pathol. 2014;27:1438–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Mencia-Trinchant N, Hu Y, Alas MA, Ali F, Wouters BJ, Lee S, et al. Minimal residual disease monitoring of acute myeloid leukemia by massively multiplex digital PCR in patients with NPM1 mutations. J Mol Diagn. 2017;19:537–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Stahl T, Böhme MU, Kröger N, Fehse B. Digital PCR to assess hematopoietic chimerism after allogeneic stem cell transplantation. Exp Hematol. 2015;43:462–8. e1

    Article  CAS  PubMed  Google Scholar 

  47. Huggett JF, Whale A. Digital PCR as a novel technology and its potential implications for molecular diagnostics. Clin Chem. 2013;59:1691–3.

    Article  CAS  PubMed  Google Scholar 

  48. Höllein A, Meggendorfer M, Dicker F, Jeromin S, Nadarajah N, Kern W, et al. NPM1 mutated AML can relapse with wild-type NPM1: persistent clonal hematopoiesis can drive relapse. Blood Adv. 2018;2:3118–25.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Cocciardi S, Dolnik A, Kapp-Schwoerer S, Rücker FG, Lux S, Blätte TJ, et al. Clonal evolution patterns in acute myeloid leukemia with NPM1 mutation. Nat Commun. 2019;10:2031.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Patkar N, Kodgule R, Kakirde C, Raval G, Bhanshe P, Joshi S, et al. Clinical impact of measurable residual disease monitoring by ultradeep next generation sequencing in NPM1 mutated acute myeloid leukemia. Oncotarget. 2018;9:36613–24.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Dillon LW, Gui G, Page KM, Ravindra N, Wong ZC, Andrew G, et al. DNA sequencing to detect residual disease in adults with acute myeloid leukemia prior to hematopoietic cell transplant. JAMA. 2023;329:745–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Zhou Y, Othus M, Walter RB, Estey EH, Wu D, Wood BL. Deep NPM1 sequencing following allogeneic hematopoietic cell transplantation improves risk assessment in adults with NPM1-mutated AML. Biol Blood Marrow Transpl. 2018;24:1615–20.

    Article  CAS  Google Scholar 

  53. Schuurhuis GJ, Heuser M, Freeman S, Béné MC, Buccisano F, Cloos J, et al. Minimal/measurable residual disease in AML: a consensus document from the European LeukemiaNet MRD working party. Blood. 2018;131:1275–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Delsing Malmberg E, Johansson Alm S, Nicklasson M, Lazarevic V, Ståhlman S, Samuelsson T, et al. Minimal residual disease assessed with deep sequencing of NPM1 mutations predicts relapse after allogeneic stem cell transplant in AML. Leuk Lymphoma. 2019;60:409–17.

    Article  CAS  PubMed  Google Scholar 

  55. Schnittger S, Kern W, Tschulik C, Weiss T, Dicker F, Falini B, et al. Minimal residual disease levels assessed by NPM1 mutation-specific RQ-PCR provide important prognostic information in AML. Blood. 2009;114:2220–31.

    Article  CAS  PubMed  Google Scholar 

  56. Lambert J, Lambert J, Nibourel O, Pautas C, Hayette S, Cayuela JM, et al. MRD assessed by WT1 and NPM1 transcript levels identifies distinct outcomes in AML patients and is influenced by gemtuzumab ozogamicin. Oncotarget. 2014;5:6280–8.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Shayegi N, Kramer M, Bornhäuser M, Schaich M, Schetelig J, Platzbecker U, et al. The level of residual disease based on mutant NPM1 is an independent prognostic factor for relapse and survival in AML. Blood. 2013;122:83–92.

    Article  CAS  PubMed  Google Scholar 

  58. Tiong IS, Dillon R, Ivey A, Kuzich JA, Thiagarajah N, Sharplin KM, et al. Clinical impact of NPM1-mutant molecular persistence after chemotherapy for acute myeloid leukemia. Blood Adv. 2021;5:5107–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Scott S, Dillon R, Thiede C, Sadiq S, Cartwright A, Clouston HJ, et al. Assessment of acute myeloid leukemia molecular measurable residual disease testing in an interlaboratory study. Blood Adv. 2023;7:3686–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Angenendt L, Röllig C, Montesinos P, Martínez-Cuadrón D, Barragan E, García R, et al. Chromosomal abnormalities and prognosis in NPM1-mutated acute myeloid leukemia: a pooled analysis of individual patient data from nine international cohorts. J Clin Oncol. 2019;37:2632–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Eckardt J-N, Bill M, Rausch C, Metzeler K, Spiekermann K, Stasik S, et al. Secondary-type mutations do not impact outcome in NPM1-mutated acute myeloid leukemia – implications for the European LeukemiaNet risk classification. Leukemia. 2023;37:2282–5.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Wright MF, Pozdnyakova O, Hasserjian RP, Aggarwal N, Shaver AC, Weinberg OK, et al. Secondary-type mutations do not impact prognosis in acute myelogenous leukemia AML with mutated NPM1. Am J Hematol. 2022;97:E462–5.

    Article  CAS  PubMed  Google Scholar 

  63. Wang Y, Quesada AE, Zuo Z, Medeiros LJ, Yin CC, Li S, et al. The impact of mutation of myelodysplasia-related genes in de novo acute myeloid leukemia carrying NPM1 mutation. Cancers. 2022;15:198.

  64. Zhao D, Zarif M, Eladl E, Capo-Chichi JM, Smith AC, Atenafu EG, et al. NPM1-mutated AML-MRC diagnosed on the basis of history of MDS or MDS/MPN frequently harbours secondary-type mutations and confers inferior outcome compared to AML with mutated NPM1. Leuk Res. 2022;118:106869.

    Article  CAS  PubMed  Google Scholar 

  65. Othman J, Potter N, Ivey A, Jovanovic J, Freeman SD, Gilkes A, et al. The benefit of allogeneic transplant in 1st complete remission in NPM1 mutated AML with or without FLT3 ITD is restricted to those testing MRD positive after induction - an analysis of the UK NCRI AML17 and AML19 studies. Blood. 2023;142:425.

    Article  Google Scholar 

  66. Lussana F, Caprioli C, Stefanoni P, Pavoni C, Spinelli O, Buklijas K, et al. Molecular detection of minimal residual disease before allogeneic stem cell transplantation predicts a high incidence of early relapse in adult patients with NPM1 positive acute myeloid leukemia. Cancers. 2019;11:1455.

  67. Hourigan CS, Dillon LW, Gui G, Ravindra N, Wong Z, Andrew G, et al. Pre-MEASURE: multicenter evaluation of the prognostic significance of measurable residual disease testing prior to allogeneic transplantation for adult patients with AML in first remission. J Clin Oncol. 2022;40:7006.

    Article  Google Scholar 

  68. Dillon R, Hills R, Freeman S, Potter N, Jovanovic J, Ivey A, et al. Molecular MRD status and outcome after transplantation in NPM1-mutated AML. Blood. 2020;135:680–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Fraccaroli A, Stauffer E, Koch K, Hirschbühl K, Breitkopf S, Ziemann F, et al. Presence of measurable residual disease in NPM1 positive AML in remission pre-transplant does not impact on survival after allogeneic hematopoietic stem cell transplantation. Blood. 2022;140:4882–3.

    Article  Google Scholar 

  70. Jimenez-Chillon C, Othman J, Taussig D, Jimenez-Vicente C, Martinez-Roca A, Tiong IS, et al. Venetoclax–based low intensity therapy in molecular failure of NPM1-mutated AML. Blood Adv. 2024;8:343–52.

    Article  CAS  PubMed  Google Scholar 

  71. Tiong IS, Dillon R, Ivey A, Teh TC, Nguyen P, Cummings N, et al. Venetoclax induces rapid elimination of NPM1 mutant measurable residual disease in combination with low-intensity chemotherapy in acute myeloid leukaemia. Br J Haematol. 2021;192:1026–30.

    Article  CAS  PubMed  Google Scholar 

  72. Tiong IS, Hiwase DK, Abro E, Bajel A, Palfreyman E, Beligaswatte A, et al. Targeting molecular measurable residual disease and low-blast relapse in AML with venetoclax and low-dose cytarabine: a prospective phase II study (VALDAC). J Clin Oncol. 2024;42:2161–73.

    Article  CAS  PubMed  Google Scholar 

  73. Bastos-Oreiro M, Perez-Corral A, Martínez-Laperche C, Bento L, Pascual C, Kwon M, et al. Prognostic impact of minimal residual disease analysis by flow cytometry in patients with acute myeloid leukemia before and after allogeneic hemopoietic stem cell transplantation. Eur J Haematol. 2014;93:239–46.

    Article  PubMed  Google Scholar 

  74. Bacher U, Badbaran A, Fehse B, Zabelina T, Zander AR, Kröger N. Quantitative monitoring of NPM1 mutations provides a valid minimal residual disease parameter following allogeneic stem cell transplantation. Exp Hematol. 2009;37:135–42.

    Article  CAS  PubMed  Google Scholar 

  75. Bill M, Grimm J, Jentzsch M, Kloss L, Goldmann K, Schulz J, et al. Digital droplet PCR-based absolute quantification of pre-transplant NPM1 mutation burden predicts relapse in acute myeloid leukemia patients. Ann Hematol. 2018;97:1757–65.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. These authors contributed equally: Mary R. Christopher, Mariam T. Nawas.

Authors and Affiliations

  1. Charité-Universitätsmedizin Berlin, Berlin, Germany

    Mary R. Christopher

  2. Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA

    Mariam T. Nawas

  3. Division of Hematology and Oncology, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI, USA

    John L. Reagan

Authors
  1. Mary R. Christopher
    View author publications

    Search author on:PubMed Google Scholar

  2. Mariam T. Nawas
    View author publications

    Search author on:PubMed Google Scholar

  3. John L. Reagan
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Contribution: MTN and MRC. performed literature review and wrote the manuscript. JLR edited the manuscript and contributed to the figures.

Corresponding author

Correspondence to Mariam T. Nawas.

Ethics declarations

Competing interests

MRC and MTN have no disclosures. JLR reports serving as a consultant and/or advisory board member for Sanofi and Bristol Myers Squibb; research support from Pfizer.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Christopher, M.R., Nawas, M.T. & Reagan, J.L. Molecular measurable residual disease monitoring and transplant indications in NPM1 mutated acute myeloid leukemia. Bone Marrow Transplant 60, 135–143 (2025). https://doi.org/10.1038/s41409-024-02465-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41409-024-02465-2

Search

Advanced search

Quick links