Advanced

Induction of blood-circulating bile acids supports recovery from myelosuppressive chemotherapy

Sigurdsson, Valgardur LU ; Haga, Youichi LU ; Takei, Hajime ; Mansell, Els LU ; Okamatsu-Haga, Chizuko ; Suzuki, Mitsuyoshi LU ; Radulovic, Visnja LU ; van der Garde, Mark LU ; Koide, Shuhei LU and Soboleva, Svetlana LU , et al. (2020) In Blood Advances 4(9). p.1833-1843
Abstract

Chemotherapeutic agents can reduce bone marrow (BM) activity, causing myelosuppression, a common life-threatening complication of cancer treatment. It is challenging to predict the patients in whom prolonged myelosuppression will occur, resulting in a delay or discontinuation of the treatment protocol. An early indicator of recovery from myelosuppression would thus be highly beneficial in clinical settings. In this study, bile acids (BAs) were highly increased in the systemic circulation as a natural response during recovery from myelosuppression, supporting regeneration of BM cells. BA levels in the blood of pediatric cancer patients and mice treated with chemotherapeutic agents were increased, in synchrony with early proliferation of... (More)

Chemotherapeutic agents can reduce bone marrow (BM) activity, causing myelosuppression, a common life-threatening complication of cancer treatment. It is challenging to predict the patients in whom prolonged myelosuppression will occur, resulting in a delay or discontinuation of the treatment protocol. An early indicator of recovery from myelosuppression would thus be highly beneficial in clinical settings. In this study, bile acids (BAs) were highly increased in the systemic circulation as a natural response during recovery from myelosuppression, supporting regeneration of BM cells. BA levels in the blood of pediatric cancer patients and mice treated with chemotherapeutic agents were increased, in synchrony with early proliferation of BM cells and recovery from myelosuppression. In a mouse model of altered BA composition, Cyp8b1 knockout mice, a subset of mice recovered poorly after chemotherapy. The poor recovery correlated with low levels and changes in composition of BAs in the liver and systemic circulation. Conversely, BA supplementation in chemotherapy-treated wild-type mice resulted in significantly improved recovery. The results suggest that part of the mechanism by which BAs support recovery is the suppression of endoplasmic reticulum stress pathways in expanding and recovering hematopoietic cells. The findings propose a novel role of BAs as early markers of recovery and active components of the recovery process after chemotherapy.

(Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood Advances
volume
4
issue
9
pages
11 pages
publisher
American Society of Hematology
external identifiers
  • scopus:85085499879
  • pmid:32365188
ISSN
2473-9529
DOI
10.1182/bloodadvances.2019000133
language
English
LU publication?
yes
id
18d21864-9a0b-46d2-a41d-645fae07a510
date added to LUP
2020-06-16 16:39:27
date last changed
2020-06-17 09:23:03
@article{18d21864-9a0b-46d2-a41d-645fae07a510,
  abstract     = {<p>Chemotherapeutic agents can reduce bone marrow (BM) activity, causing myelosuppression, a common life-threatening complication of cancer treatment. It is challenging to predict the patients in whom prolonged myelosuppression will occur, resulting in a delay or discontinuation of the treatment protocol. An early indicator of recovery from myelosuppression would thus be highly beneficial in clinical settings. In this study, bile acids (BAs) were highly increased in the systemic circulation as a natural response during recovery from myelosuppression, supporting regeneration of BM cells. BA levels in the blood of pediatric cancer patients and mice treated with chemotherapeutic agents were increased, in synchrony with early proliferation of BM cells and recovery from myelosuppression. In a mouse model of altered BA composition, Cyp8b1 knockout mice, a subset of mice recovered poorly after chemotherapy. The poor recovery correlated with low levels and changes in composition of BAs in the liver and systemic circulation. Conversely, BA supplementation in chemotherapy-treated wild-type mice resulted in significantly improved recovery. The results suggest that part of the mechanism by which BAs support recovery is the suppression of endoplasmic reticulum stress pathways in expanding and recovering hematopoietic cells. The findings propose a novel role of BAs as early markers of recovery and active components of the recovery process after chemotherapy.</p>},
  author       = {Sigurdsson, Valgardur and Haga, Youichi and Takei, Hajime and Mansell, Els and Okamatsu-Haga, Chizuko and Suzuki, Mitsuyoshi and Radulovic, Visnja and van der Garde, Mark and Koide, Shuhei and Soboleva, Svetlana and Gåfvels, Mats and Nittono, Hiroshi and Ohara, Akira and Miharada, Kenichi},
  issn         = {2473-9529},
  language     = {eng},
  month        = {05},
  number       = {9},
  pages        = {1833--1843},
  publisher    = {American Society of Hematology},
  series       = {Blood Advances},
  title        = {Induction of blood-circulating bile acids supports recovery from myelosuppressive chemotherapy},
  url          = {http://dx.doi.org/10.1182/bloodadvances.2019000133},
  doi          = {10.1182/bloodadvances.2019000133},
  volume       = {4},
  year         = {2020},
}