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Lookup NU author(s): Dr Simon BomkenORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Relapsed acute leukemia can be difficult to salvage. An uncommon but increasingly recognized and aggressive mechanism of relapse involves lineage switch. In lineage switch, the immunophenotype of the leukemia at relapse differs from the immunophenotype at initial diagnosis, with the underlying genetic driver(s) conserved, confirming a clonal relationship. Lineage switch is most common – and was first recognized – in B-cell acute lymphoblastic leukemia with KMT2A rearrangement, which often relapses as acute myeloid leukemia. In an era where antigen-targeted therapies, including chimeric antigen receptor T-cells and bispecific T-cell engagers, are increasingly utilized and thus apply selective antigen pressure, this may increase the incidence of lineage switch across different leukemia subtypes. Patients with lineage switch have dismal outcomes and optimal therapies remain unknown, thus there is a large unmet need to better understand the biology, define the diagnosis, and determine the therapeutic approaches to lineage switch. Here, we address these needs providing a review of the current biology of lineage switch, the relationship to different genetic subtypes and present definitions and recommendations for immunophenotypic and molecular monitoring.
Author(s): Kovach AE, Ding YY, Lamble AJ, Bernt K, Bomken S, Broderson LE, Buldini B, Delgado Colon D, Coorens THH, Green Gladden R, Gu Z, Hu S, Jacoby E, Janssens D, Kurzer JH, Mejstrikova E, Raiker SS, Rheingold SR, Silbert SK, Tan K, Yuan CM, Wang HW, Ghorashian S, Shah NN, Davis KL
Publication type: Article
Publication status: Published
Journal: Leukemia
Year: 2026
Pages: epub ahead of print
Online publication date: 26/06/2026
Acceptance date: 12/06/2026
Date deposited: 22/06/2026
ISSN (print): 0887-6924
ISSN (electronic): 1476-5551
Publisher: Nature Publishing Group
URL: https://doi.org/10.1038/s41375-026-03020-2
DOI: 10.1038/s41375-026-03020-2
ePrints DOI: 10.57711/wz9m-4c26
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