
Histamine receptor 1 is expressed in leukaemic cells and affects differentiation sensitivity
Author(s) -
CornetMasana Josep M.,
BanúsMulet Antònia,
CuestaCasanovas Laia,
Carbó José M.,
Guijarro Francesca,
Torrente Miguel Ángel,
Esteve Jordi,
Risueño Ruth M.
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15930
Subject(s) - myeloid , haematopoiesis , histamine , mapk/erk pathway , retinoic acid , biology , cancer research , receptor , cellular differentiation , immune system , immunology , stem cell , microbiology and biotechnology , kinase , pharmacology , cell culture , biochemistry , genetics , gene
Despite the success of immunotherapy in several haematological neoplasms, the effectiveness in acute myeloid leukaemia (AML) is still controversial, partially due to the lack of knowledge regarding immune‐related processes in this disease and similar neoplasias. In this study, we analysed the role and expression of histamine receptor 1 (HRH1) in haematological malignancies. Although the histamine receptor type 1 was widely expressed in healthy and malignant haematopoiesis, especially along the myeloid lineage, HRH1 lacked a relevant role in survival/proliferation and chemoresistance of AML cells, as analysed by HRH1 knockdown (KD) and pharmacological modulation. However, HRH1‐mediated signalling was critical for the activation of the differentiation process induced by several agents including all‐trans retinoic acid, establishing a role for HRH1 in myeloid differentiation. Pharmacological activation of Erk was able to partially restore differentiation capacity in HRH1 KD AML cells, suggesting that HRH1 signalling acts upstream MAPK‐Erk pathway. As an indirect consequence of our results, treatment‐related histamine release is not expected to confer a proliferative advantage in leukaemic cells.