Molecular characterization of V(D)J rearrangements in immature acute leukemias.

Autor: Vianna DT; Biological Molecular Laboratory, Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brazil; Pediatric Hematology Service, Institute of Pediatrics and Childcare Martagão Gesteira (IPPMG), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil. Electronic address: dvianna@inca.gov.br., Reis Monte-Mór BDC; Biological Molecular Laboratory, Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brazil., Noronha EP; Cell Processing, Hematology and Hemotherapy Supervision Center of Maranhão (HEMOMAR), São Luís, Maranhão, Brazil., Gutiyama LM; Biological Molecular Laboratory, Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brazil., da Costa ES; Pediatrics Department, Faculty of Medicine, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil., Pombo-de-Oliveira MS; Research Center, Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brazil., Zalcberg I; Biological Molecular Laboratory, Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brazil.
Jazyk: angličtina
Zdroj: Leukemia research [Leuk Res] 2024 Aug; Vol. 143, pp. 107521. Date of Electronic Publication: 2024 Jun 03.
DOI: 10.1016/j.leukres.2024.107521
Abstrakt: Early T-cell Precursor Acute Lymphoblastic Leukemia (ETP-ALL), T-Lymphoid/Myeloid Mixed Phenotype Acute Leukemia (T/M-MPAL), and Acute Myeloid Leukemia with minimal differentiation (AML-M0) are immature acute leukemias (AL) that present overlapping T-cell lymphoid and myeloid features at different degrees, with impact to disease classification. An interesting strategy to assess lymphoid lineage commitment and maturation is the analysis of V(D)J gene segment recombination, which can be applied to investigate leukemic cells in immature AL. Herein, we revisited 19 ETP-ALL, 8 T/M-MPAL, and 12 AML-M0 pediatric patients to characterize V(D)J rearrangement (V(D)J-r) profiles associated with other somatic alterations. V(D)J-r were identified in 74 %, 25 %, and 25 % of ETP-ALL, T/M-MPAL, and AML-M0, respectively. Forty-six percent of ETP-ALL harbored ≥ 3 V(D)J-r, while there was no more than one V(D)J-r per patient in AML-M0 and T/M-MPAL. TCRD was the most rearranged locus in ETPALL, but it was not rearranged in other AL. In ETP-ALL, N/KRAS mutations were associated with absence of V(D)J-r, while NF1 deletion was most frequent in patients with ≥ 3 V(D)J-r. Relapse and death occurred mainly in patients harboring one or no rearranged locus. Molecular characterization of V(D)J-r in our cohort indicates a distinct profile of ETP-ALL, compared to T/M-MPAL and AML-M0. Our findings also suggest that the clinical outcome of ETP-ALL patients may be affected by blast cell maturity, inferred from the number of rearranged TCR loci.
Competing Interests: Declaration of Competing Interest The authors have nothing to disclose.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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