Multiple myeloma hinders erythropoiesis and causes anaemia owing to high levels of CCL3 in the bone marrow microenvironment

Abstract Anaemia is the most common complication of myeloma and is associated with worse clinical outcomes. Although marrow replacement with myeloma cells is widely considered a mechanistic rationale for anaemia, the exact process has not been fully understood. Our large cohort of 1363 myeloma patie...

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Autores principales:	Lanting Liu, Zhen Yu, Hui Cheng, Xuehan Mao, Weiwei Sui, Shuhui Deng, Xiaojing Wei, Junqiang Lv, Chenxing Du, Jie Xu, Wenyang Huang, Shuang Xia, Gang An, Wen Zhou, Xiaoke Ma, Tao Cheng, Lugui Qiu, Mu Hao
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0df5feab60dc4b5bb3eb81cecc9122ff
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spelling	oai:doaj.org-article:0df5feab60dc4b5bb3eb81cecc9122ff2021-12-02T12:33:53ZMultiple myeloma hinders erythropoiesis and causes anaemia owing to high levels of CCL3 in the bone marrow microenvironment10.1038/s41598-020-77450-y2045-2322https://doaj.org/article/0df5feab60dc4b5bb3eb81cecc9122ff2020-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-77450-yhttps://doaj.org/toc/2045-2322Abstract Anaemia is the most common complication of myeloma and is associated with worse clinical outcomes. Although marrow replacement with myeloma cells is widely considered a mechanistic rationale for anaemia, the exact process has not been fully understood. Our large cohort of 1363 myeloma patients had more than 50% of patients with moderate or severe anaemia at the time of diagnosis. Anaemia positively correlated with myeloma cell infiltration in the bone marrow (BM) and worse patient outcomes. The quantity and erythroid differentiation of HSPCs were affected by myeloma cell infiltration in the BM. The master regulators of erythropoiesis, GATA1 and KLF1, were obviously downregulated in myeloma HSPCs. However, the gene encoding the chemokine CCL3 showed significantly upregulated expression. Elevated CCL3 in the BM plasma of myeloma further inhibited the erythropoiesis of HSPCs via activation of CCL3/CCR1/p38 signalling and suppressed GATA1 expression. Treatment with a CCR1 antagonist effectively recovered GATA1 expression and rescued erythropoiesis in HSPCs. Myeloma cell infiltration causes elevated expression of CCL3 in BM, which suppresses the erythropoiesis of HSPCs and results in anaemia by downregulating the level of GATA1 in HSPCs. Thus, our study indicates that targeting CCL3 would be a potential strategy against anaemia and improve the survival of myeloma patients.Lanting LiuZhen YuHui ChengXuehan MaoWeiwei SuiShuhui DengXiaojing WeiJunqiang LvChenxing DuJie XuWenyang HuangShuang XiaGang AnWen ZhouXiaoke MaTao ChengLugui QiuMu HaoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-14 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lanting Liu Zhen Yu Hui Cheng Xuehan Mao Weiwei Sui Shuhui Deng Xiaojing Wei Junqiang Lv Chenxing Du Jie Xu Wenyang Huang Shuang Xia Gang An Wen Zhou Xiaoke Ma Tao Cheng Lugui Qiu Mu Hao Multiple myeloma hinders erythropoiesis and causes anaemia owing to high levels of CCL3 in the bone marrow microenvironment
description	Abstract Anaemia is the most common complication of myeloma and is associated with worse clinical outcomes. Although marrow replacement with myeloma cells is widely considered a mechanistic rationale for anaemia, the exact process has not been fully understood. Our large cohort of 1363 myeloma patients had more than 50% of patients with moderate or severe anaemia at the time of diagnosis. Anaemia positively correlated with myeloma cell infiltration in the bone marrow (BM) and worse patient outcomes. The quantity and erythroid differentiation of HSPCs were affected by myeloma cell infiltration in the BM. The master regulators of erythropoiesis, GATA1 and KLF1, were obviously downregulated in myeloma HSPCs. However, the gene encoding the chemokine CCL3 showed significantly upregulated expression. Elevated CCL3 in the BM plasma of myeloma further inhibited the erythropoiesis of HSPCs via activation of CCL3/CCR1/p38 signalling and suppressed GATA1 expression. Treatment with a CCR1 antagonist effectively recovered GATA1 expression and rescued erythropoiesis in HSPCs. Myeloma cell infiltration causes elevated expression of CCL3 in BM, which suppresses the erythropoiesis of HSPCs and results in anaemia by downregulating the level of GATA1 in HSPCs. Thus, our study indicates that targeting CCL3 would be a potential strategy against anaemia and improve the survival of myeloma patients.
format	article
author	Lanting Liu Zhen Yu Hui Cheng Xuehan Mao Weiwei Sui Shuhui Deng Xiaojing Wei Junqiang Lv Chenxing Du Jie Xu Wenyang Huang Shuang Xia Gang An Wen Zhou Xiaoke Ma Tao Cheng Lugui Qiu Mu Hao
author_facet	Lanting Liu Zhen Yu Hui Cheng Xuehan Mao Weiwei Sui Shuhui Deng Xiaojing Wei Junqiang Lv Chenxing Du Jie Xu Wenyang Huang Shuang Xia Gang An Wen Zhou Xiaoke Ma Tao Cheng Lugui Qiu Mu Hao
author_sort	Lanting Liu
title	Multiple myeloma hinders erythropoiesis and causes anaemia owing to high levels of CCL3 in the bone marrow microenvironment
title_short	Multiple myeloma hinders erythropoiesis and causes anaemia owing to high levels of CCL3 in the bone marrow microenvironment
title_full	Multiple myeloma hinders erythropoiesis and causes anaemia owing to high levels of CCL3 in the bone marrow microenvironment
title_fullStr	Multiple myeloma hinders erythropoiesis and causes anaemia owing to high levels of CCL3 in the bone marrow microenvironment
title_full_unstemmed	Multiple myeloma hinders erythropoiesis and causes anaemia owing to high levels of CCL3 in the bone marrow microenvironment
title_sort	multiple myeloma hinders erythropoiesis and causes anaemia owing to high levels of ccl3 in the bone marrow microenvironment
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/0df5feab60dc4b5bb3eb81cecc9122ff
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Multiple myeloma hinders erythropoiesis and causes anaemia owing to high levels of CCL3 in the bone marrow microenvironment

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