Clonotypic VDJ rearrangements in Mixed Phenotype Acute Leukemia can be Successfully Utilized to Track Minimal Residual Disease (MRD).
Journal
Applied immunohistochemistry & molecular morphology : AIMM
ISSN: 1533-4058
Titre abrégé: Appl Immunohistochem Mol Morphol
Pays: United States
ID NLM: 100888796
Informations de publication
Date de publication:
02 May 2024
02 May 2024
Historique:
received:
18
09
2023
accepted:
01
04
2024
medline:
2
5
2024
pubmed:
2
5
2024
entrez:
2
5
2024
Statut:
aheadofprint
Résumé
Multiplex polymerase chain reaction (PCR) and next-generation sequencing (NGS) can both be used to identify a neoplastic clonotype by targeting CDR3 and assessing rearrangements in IgH, IgK, IgL, TCR-β, and TCR-gamma loci. The clonotypic sequence can be robustly used to track minimal residual disease (MRD). The ability to track MRD by NGS in mixed phenotype acute leukemia (MPAL) is unknown and warrants investigation. Institutional Review Board (IRB) approval was obtained. Central Moffitt Cancer Center (MCC) database was searched to locate any patients with MPAL from over 600,000 entries. Patient charts were manually curated to identify those with clonoSEQ data, and clinical data was procured from the electronic medical record (EMR). Twenty-nine patients with MPAL were identified. Only 2 patients with clonoSEQ testing were found. Both demonstrated a B/myeloid phenotype, and both were bilineal. NGS (clonoSEQ) identified 4 dominant (IGH) (patient A; 8/2019) and 2 dominant sequences (patient B; 10/2019), respectively. In both patients, clonoSEQ testing successfully tracked minimal residual disease and mirrored clinical disease burden. This report is the first to confirm the utility of NGS-based MRD tracking in patients with MPAL and shows increased sensitivity of NGS over MRD flow cytometry.
Identifiants
pubmed: 38695552
doi: 10.1097/PAI.0000000000001203
pii: 00129039-990000000-00172
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
Références
Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391–2405. Blood, 2016;128:462-463.
Weinberg OK, Arber DA, Döhner H, et al. The International Consensus Classification of acute leukemias of ambiguous lineage. Blood. 2023;141:2275–2277.
Hussaini MO, Srivastava J, Lee LW, et al. Assessment of clonotypic rearrangements and minimal residual disease in lymphoid malignancies. Arch Pathol Lab Med. 2022;146:485–493.
Kyoda K, Nakamura S, Matano S, et al. Prognostic significance of immunoglobulin heavy chain gene rearrangement in patients with acute myelogenous leukemia. Leukemia. 1997;11:803–806.
Dyer MJS, Hoyle CF, Rees JKH, et al. T-Cell receptor and immunoglobulin gene rearrangements in acute myeloid and undifferentiated leukemias of adults: Correlation with weak surface expression of CD45 and CDw52 Antigens. Leuk Lymphoma. 1991;3:257–265.
Saygin C, Cannova J, Stock W, et al. Measurable residual disease in acute lymphoblastic leukemia: Methods and clinical context in adult patients. Haematologica. 2022;107:2783–2793.
Logan AC, Vashi N, Faham M, et al. Immunoglobulin and T cell receptor gene high-throughput sequencing quantifies minimal residual disease in acute lymphoblastic leukemia and predicts post-transplantation relapse and survival. Biol Blood Marrow Transplant. 2014;20:1307–1313.
Martinez-Lopez J, Lahuerta JJ, Pepin F, et al. Prognostic value of deep sequencing method for minimal residual disease detection in multiple myeloma. Blood. 2014;123:3073–3079.
Oberley MJ, Raikar SS, Wertheim GB, et al. Significance of minimal residual disease in pediatric mixed phenotype acute leukemia: A multicenter cohort study. Leukemia. 2020;34:1741–1750.
Wolach O, Stone RM. How I treat mixed-phenotype acute leukemia. Blood. 2015;125:2477–2485.