Replenishment of the B cell compartment after doxorubicin-induced hematopoietic toxicity is facilitated by STAT1. Issue 6 (1st June 2014)

• Record Type: Journal Article
• Authors: Datta, Sebak; Parajuli, Nirmala; Tymoszuk, Piotr; Ottina, Eleonora; Parson, Walther; Sgonc, Roswitha; Villunger, Andreas; Doppler, Wolfgang
• Is Part Of: Journal of leukocyte biology. Volume 95:Issue 6(2014)
• Page Start: 853
• Page End: 866
• Publication Date: 2014-06-01
• Subjects: lymphocyte development -- pro-B cells -- Sca-1 -- IFN-γ -- IL-7; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.0113053
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : Lymphoid development before differentiation to pre-B cells is impaired in STAT1-deficient mice, and apparent in the recovery phase of doxorubicin-induced hematopoietic toxicity. Abstract: STAT1 serves as an important regulator in the response to pathogens, oncogenic transformation, and genotoxic insults. It exerts these effects by shaping the innate and adaptive immune response and by participating in genotoxic stress pathways, leading to apoptosis and inhibition of cell proliferation. We have investigated the role of STAT1 in hematopoietic toxicity induced by doxorubicin in STAT1-proficient and -deficient mice. Whereas the early genotoxic effect of doxorubicin did not depend on STAT1, expression of STAT1 was required for efficient B lymphocyte repopulation in the recovery phase. We found a lower abundance of lymphocyte precursors in the BM of STAT1-deficient animals, which was particularly evident after doxorubicin-induced hematopoietic toxicity. In accordance, colony-forming assays with STAT1-deficient BM cells revealed a decreased number of pre-B colonies. Differentiation from the pro-B to the pre-B stage was not affected, as demonstrated by unaltered differentiation of purified B cell precursors from BM in the presence of IL-7. With the exception of Sca-1, expression of genes implicated in early lymphocyte development in pro-B cells did not depend on STAT1. Our findings indicate a specific requirement for STAT1 in lymphoid development before differentiation to pre-B cells, which becomes particularly apparent in the recovery phase from doxorubicin-induced hematopoietic toxicity.