Chronic lymphocytic leukemia B-cell-derived TNFα impairs bone marrow myelopoiesis.
iScience
; 24(1): 101994, 2021 Jan 22.
Article
em En
| MEDLINE
| ID: mdl-33458625
ABSTRACT
TNFα is implicated in chronic lymphocytic leukemia (CLL) immunosuppression and disease progression. TNFα is constitutively produced by CLL B cells and is a negative regulator of bone marrow (BM) myelopoiesis. Here, we show that co-culture of CLL B cells with purified normal human hematopoietic stem and progenitor cells (HSPCs) directly altered protein levels of the myeloid and erythroid cell fate determinants PU.1 and GATA-2 at the single-cell level within transitional HSPC subsets, mimicking ex vivo expression patterns. Physical separation of CLL cells from control HSPCs or neutralizing TNFα abrogated upregulation of PU.1, yet restoration of GATA-2 required TNFα neutralization, suggesting both cell contact and soluble-factor-mediated regulation. We further show that CLL patient BM myeloid progenitors are diminished in frequency and function, an effect recapitulated by chronic exposure of control HSPCs to low-dose TNFα. These findings implicate CLL B-cell-derived TNFα in impaired BM myelopoiesis.
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Base de dados:
MEDLINE
Idioma:
En
Revista:
IScience
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos