RESUMO
OBJECTIVES: This study aims to retrospectively assess C-lectin-like molecule 1 (CLL-1) bimodal expression on CD34+ blasts in acute myeloid leukemia (AML) patients (total N = 306) and explore potential CLL-1 bimodal associations with leukemia and patient-specific characteristics. METHODS: Flow cytometry assays were performed to assess the deeper immunophenotyping of CLL-1 bimodality. Cytogenetic analysis was performed to characterize the gene mutation on CLL-1-negative subpopulation of CLL-1 bimodal AML samples. RESULTS: The frequency of a bimodal pattern of CLL-1 expression of CD34+ blasts ranged from 8% to 65% in the different cohorts. Bimodal CLL-1 expression was most prevalent in patients with MDS-related AML (P = .011), ELN adverse risk (P = .002), NPM1 wild type (WT, P = .049), FLT3 WT (P = .035), and relatively low percentages of leukemia-associated immunophenotypes (P = .006). Additional immunophenotyping analysis revealed the CLL-1- subpopulation may consist of pre-B cells, immature myeloblasts, and hematopoietic stem cells. Furthermore, (pre)-leukemic mutations were detected in both CLL-1+ and CLL-1- subfractions of bimodal samples (N = 3). CONCLUSIONS: C-lectin-like molecule 1 bimodality occurs in about 25% of AML patients and the CLL-1- cell population still contains malignant cells, hence it may potentially limit the effectiveness of CLL-1-targeted therapies and warrant further investigation.
Assuntos
Biomarcadores Tumorais/genética , Células da Medula Óssea/metabolismo , Lectinas Tipo C/genética , Leucemia Mieloide Aguda/genética , Mutação , Células Mieloides/metabolismo , Receptores Mitogênicos/genética , Antígenos CD34/genética , Antígenos CD34/imunologia , Biomarcadores Tumorais/imunologia , Células da Medula Óssea/imunologia , Células da Medula Óssea/patologia , Análise Citogenética , Feminino , Citometria de Fluxo , Perfilação da Expressão Gênica , Regulação Leucêmica da Expressão Gênica , Células-Tronco Hematopoéticas/imunologia , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/patologia , Humanos , Imunofenotipagem , Lectinas Tipo C/imunologia , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Células Mieloides/imunologia , Células Mieloides/patologia , Células Precursoras de Linfócitos B/imunologia , Células Precursoras de Linfócitos B/metabolismo , Células Precursoras de Linfócitos B/patologia , Cultura Primária de Células , Receptores Mitogênicos/imunologiaRESUMO
Although many studies are focused on auto-reactive CD4(+) T cells, the precise role of CD8(+) T cells in autoimmunity is poorly understood. The objective of this study is to provide more insight into the phenotype and function CD8(+) T cells during the development of autoimmune disease by studying CD8(+) T cells in human lymph-node biopsies and peripheral blood obtained during the earliest phases of rheumatoid arthritis (RA). Here, we show that lymphoid pro-inflammatory CD8(+) T cells exhibit a less-responsive phenotype already during the earliest phases of autoimmunity compared with healthy individuals. We found an increase in CD8(+) memory T cells in lymphoid tissue during the earliest phases of autoimmunity, even before clinical onset of RA, accompanied by an increased frequency of non-circulating or recently activated (CD69(+)) CD8(+) T cells in lymphoid tissue and peripheral blood. Importantly, lymphoid pro-inflammatory CD8(+)IL-17A(+) T cells displayed a decreased capacity of cytokine production, which was related to disease activity in early RA patients. In addition, a decreased frequency of regulatory CD8(+)IL-10(+) T cells in peripheral blood was also related to disease activity in early RA patients. Our results suggest that different CD8(+) T-cell subsets are affected already during the earliest phases of systemic autoimmunity.
