Document Type
Article
Publication Date
4-23-2024
Identifier
DOI: 10.1182/bloodadvances.2023010805; PMCID: PMC11024924
Abstract
MLLT10 gene rearrangements with KMT2A occur in pediatric acute myeloid leukemia (AML) and confer poor prognosis, but the prognostic impact of MLLT10 in partnership with other genes is unknown. We conducted a retrospective study with 2080 children and young adults with AML registered on the Children's Oncology Group AAML0531 (NCT00372593) and AAML1031 trials (NCT01371981). Transcriptome profiling and/or karyotyping were performed to identify leukemia-associated fusions associated with prognosis. Collectively, 127 patients (6.1%) were identified with MLLT10 fusions: 104 (81.9%) with KMT2A::MLLT10, 13 (10.2%) with PICALM::MLLT10, and 10 (7.9%) X::MLLT10: (2 each of DDX3X and TEC), with 6 partners (DDX3Y, CEP164, SCN2B, TREH, NAP1L1, and XPO1) observed in single patients. Patients with MLLT10 (n = 127) demonstrated adverse outcomes, with 5-year event-free survival (EFS) of 18.6% vs 49% in patients without MLLT10 (n = 1953, P < .001), inferior 5-year overall survival (OS) of 38.2% vs 65.7% (P ≤ .001), and a higher relapse risk of 76% vs 38.6% (P < .001). Patients with KMT2A::MLLT10 had an EFS from study entry of 19.5% vs 12.7% (P = .628), and an OS from study entry of 40.4% vs 27.6% (P = .361) in those with other MLLT10 fusion partners. Patients with PICALM::MLLT10 had an EFS of 9.2% vs 20% in other MLLT10- without PICALM (X::MLLT10; P = .788). Patients with PICALM::MLLT10 and X::MLLT10 fusions exhibit a DNA hypermethylation signature resembling NUP98::NSD1 fusions, whereas patients with KMT2A::MLLT10 bear aberrations primarily affecting distal regulatory elements. Regardless of the fusion partner, patients with AML harboring MLLT10 fusions exhibit very high-risk features and should be prioritized for alternative therapeutic interventions.
Journal Title
Blood Adv
Volume
8
Issue
8
First Page
2005
Last Page
2017
MeSH Keywords
Child; Young Adult; Humans; Retrospective Studies; Oncogene Proteins, Fusion; Transcription Factors; Leukemia, Myeloid, Acute; Prognosis; Minor Histocompatibility Antigens; DEAD-box RNA Helicases; Nucleosome Assembly Protein 1
Keywords
Retrospective Studies; Fusion Oncogene Proteins; Transcription Factors; Acute Myeloid Leukemia; Prognosis; Minor Histocompatibility Antigens; DEAD-box RNA Helicases; Nucleosome Assembly Protein 1
Recommended Citation
Abla O, Ries RE, Triche T Jr, et al. Structural variants involving MLLT10 fusion are associated with adverse outcomes in pediatric acute myeloid leukemia. Blood Adv. 2024;8(8):2005-2017. doi:10.1182/bloodadvances.2023010805
Comments
Grants and funding
Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution.
Publisher's Link: https://ashpublications.org/bloodadvances/article/8/8/2005/514803/Structural-variants-involving-MLLT10-fusion-are