Monitoring Minimal Residual Disease in RUNX1-Mutated Acute Myeloid Leukemia

Original Paper

Open Access Gateway Nachmias B.a· Krichevsky S.a· Filon D.a· Even-Or E.Gatt M.a· Saban R.a· Avni B.b· Grisariu S.b· Aumann S.a· Vainstein V.a

Author affiliations

aDepartment of Hematology, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
bDepartment of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel

Corresponding Author

Boaz Nachmias, Nachmiasb@gmail.com

Abstract

Introduction: Mutated RUNX1 is considered a poor prognostic factor and usually is mutually exclusive with NPM1 mutations. Monitoring of molecular markers for minimal residual disease provides a powerful tool to assess remission and guide clinical decisions. Methods: Newly diagnosed RUNX1-mutated AML patients, designated to intensive chemotherapy-based treatment or nonintensive regimens, were monitored for mutated RUNX1 transcript levels by qPCR with patient-specific primers. Samples were obtained along the treatment course and follow-up. Results: A clear correlation was observed between mutated RUNX1 levels and response to treatment as observed by flow cytometry and STR-based assessment. Conclusion: We demonstrate the feasibility of RUNX1-based MRD to correlate with the clinicopathological status of leukemia. We further suggest how RUNX1 qPCR monitoring can influence clinical decision-making and contribute to improved personalized patient care.

© 2022 The Author(s). Published by S. Karger AG, Basel

References Schuurhuis GJ, Heuser M, Freeman S, Béné M-C, 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(12):1275–91. Krönke J, Schlenk RF, Jensen K-O, 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 Jul;29(19):2709–16. 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 Jan;35(2):185–93. Jourdan E, Boissel N, Chevret S, Delabesse E, Renneville A, Cornillet P, et al. Prospective evaluation of gene mutations and minimal residual disease in patients with core binding factor acute myeloid leukemia. Blood. 2013 Mar;121(12):2213–23. 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 Feb;374(5):422–33. Ichikawa M, Yoshimi A, Nakagawa M, Nishimoto N, Watanabe-Okochi N, Kurokawa M. A role for RUNX1 in hematopoiesis and myeloid leukemia. Int J Hematol. 2013 Jun;97(6):726–34. Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017 Jan;129(4):424–47. Stengel A, Kern W, Meggendorfer M, Nadarajah N, Perglerovà K, Haferlach T, et al. Number of RUNX1 mutations, wild-type allele loss and additional mutations impact on prognosis in adult RUNX1-mutated AML. Leukemia. 2018;32(2):295–302. You E, Cho Y-U, Jang S, Seo E-J, Lee J-H, Lee J-H, et al. Frequency and clinicopathologic features of RUNX1 mutations in patients with acute myeloid leukemia not otherwise specified. Am J Clin Pathol. 2017 Jul;148(1):64–72. Sood R, Kamikubo Y, Liu P. Role of RUNX1 in hematological malignancies. Blood. 2017 Apr;129(15):2070–82. Kohlmann A, Nadarajah N, Alpermann T, Grossmann V, Schindela S, Dicker F, et al. Monitoring of residual disease by next-generation deep-sequencing of RUNX1 mutations can identify acute myeloid leukemia patients with resistant disease. Leukemia. 2014 Jan;28(1):129–37. Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001 May;29(9):e45. Ravandi F, Walter RB, Freeman SD. Evaluating measurable residual disease in acute myeloid leukemia. Blood Adv. 2018;2(11):1356–66. Puckrin R, Atenafu EG, Claudio JO, Chan S, Gupta V, Maze D, et al. Measurable residual disease monitoring provides insufficient lead-time to prevent morphologic relapse in the majority of patients with core-binding factor acute myeloid leukemia. Haematologica. 2021;106(1):56–63. Abou Dalle I, Jabbour E, Short NJ. Evaluation and management of measurable residual disease in acute lymphoblastic leukemia. Ther Adv Hematol. 2020;11:2040620720910023. Article / Publication Details

Received: January 10, 2022
Accepted: July 13, 2022
Published online: August 05, 2022

Number of Print Pages: 8
Number of Figures: 1
Number of Tables: 4

ISSN: 0001-5792 (Print)
eISSN: 1421-9662 (Online)

For additional information: https://www.karger.com/AHA

Figures Thumbnail Tables Thumbnail Thumbnail Thumbnail Thumbnail Open Access License / Drug Dosage / Disclaimer This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC). Usage and distribution for commercial purposes requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

留言 (0)

沒有登入
gif