RESUMO
Molecular minimal residual disease (MRD) analysis is fast emerging as an essential clinical decision-making tool for the treatment and follow-up of mature B cell malignancies. Current EuroMRD consensus IGH real-time quantitative polymerase chain reaction RQ-PCR assays rely on flow cytometric assessment of diagnostic tumour burdens to construct 'normalized', patient-specific, diagnostic DNA-based MRD quantification standards. Here, we propose a new 'hybrid' assay that relies on plasmid-based quantification of patient-specific IGH VDJ targets by consensus IGH real time (RQ)-PCR, combined with EuroMRD guidelines, for MRD monitoring in lymphoid malignancies. This assay was evaluated for MRD assessment in a total of 273 samples from 29 mantle cell lymphoma (MCL) patients treated within a Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang (GOELAMS) Phase II trial and was feasible, reliable and consistently comparable to gold-standard MRD techniques (99% concordance across all samples including 32 samples within the quantitative range) when analysed in parallel (117 samples). Integrating clinical prognostic parameters and MRD status in peripheral blood at the post-induction stage was predictive of progression-free survival (P = 0·034) thus demonstrating the clinical utility of the approach. Plasmid-based standards for the quantification of IGH VDJ targets are therefore confirmed to offer new opportunities for further standardization and clinical evaluation of MRD-guided management of patients with mature B cell malignancies.
Assuntos
Cadeias Pesadas de Imunoglobulinas/genética , Linfoma de Célula do Manto/diagnóstico , Recombinação V(D)J/genética , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linhagem Celular Tumoral , DNA de Neoplasias/genética , Intervalo Livre de Doença , Estudos de Viabilidade , Feminino , Rearranjo Gênico de Cadeia Pesada de Linfócito B/genética , Humanos , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/genética , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Plasmídeos/genética , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real/métodosRESUMO
Recent identification of CD4(+)CD56(+) malignancies as pathological counterparts of the precursors of type 2 dendritic cells (DC2) has shed new light on a leukocyte lineage that long remained elusive. This review retraces how knowledge evolved, through careful examination and analysis of both normal lymphoid tissue and rare proliferative diseases, from plasmacytoid T cells to plasmacytoid dendritic cells (pDC) and then DC2. The functions of these cells and their key role at the crossroads of innate and cognitive immunity are also discussed. The major characteristics of DC2 malignancies are summarized and compared to natural killer cell (NK) lymphomas, another type of proliferative disease sharing the expression of CD56.