The CML-related oncoprotein BCR/ABL induces expression of histidine decarboxylase (HDC) and the synthesis of histamine in leukemic cells

Aichberger, Karl J.; Mayerhofer, Matthias; Vales, Anja; Krauth, Maria Theresa; Gleixner, Karoline V.; Bilban, Martin; Esterbauer, Harald; Sonneck, Karoline; Florian, Stefan; Derdak, Sophia; Pickl, Winfried F.; Agis, Hermine; Falus, András; Sillaber, Christian; Valent, Peter

doi:10.1182/blood-2005-12-028456

Cited by 22 publications

(23 citation statements)

References 53 publications

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“…BEAS-2B cells maintain the characteristics of primary bronchial epithelial cells including expression of ICAM-1, eotaxin and CXCL8 [19][20][21], while KU812 cells constitute the phenotypes of basophils, such as histamine release and FcgammaRII expression [22]. We also used primary bronchial epithelial cells and peripheral blood basophils to confirm our findings of BEAS-2B and KU812 cells.…”

Section: Discussionsupporting

confidence: 68%

Interleukin-17A activation on bronchial epithelium and basophils: a novel inflammatory mechanism

Wong¹,

Cao²,

Yin³

et al. 2009

Eur Respir J

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Basophils are the accessory cell type for T-helper (Th)2 induction and initiators in immunoglobulin E-mediated chronic allergic inflammation. Basophils and Th17 cells accumulate at the inflammatory sites, such as the airways of allergic asthmatic patients.We investigated the activation of interleukin (IL)-17A on the primary human basophils/KU812 basophilic cells and primary human bronchial epithelial cells/BEAS-2B bronchial epithelial cells. Cytokines, chemokines, adhesion molecules and intracellular signalling molecules were assayed by ELISA or flow cytometry.Co-culture of bronchial epithelial cells and basophils could significantly induce the release of IL-6, an epithelial inflammatory cytokine, and CCL2, a chemokine for basophils, esosinophils and monocytes. Such induction was synergistically enhanced by IL-17A, and direct interaction between these two cells was necessary for IL-17A-induced IL-6 and CCL2 release. Surface expression of intercellular adhesion molecule-1 on bronchial epithelial cells was also upregulated upon their interaction. The interaction of basophils and bronchial epithelial cells under IL-17A stimulation was differentially regulated by extracellular signal-regulated kinase, c-Jun N-terminal protein kinase, p38 mitogen-activated protein kinase and nuclear factor-kB pathways.These findings suggest a novel immunopathological role of Th17 cells and basophils in allergic asthma through the activation of granulocyte-mediated inflammation initiated by the direct interaction between basophils and bronchial epithelial cells.

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Section: Discussionsupporting

confidence: 68%

Interleukin-17A activation on bronchial epithelium and basophils: a novel inflammatory mechanism

Wong¹,

Cao²,

Yin³

et al. 2009

Eur Respir J

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“…A number of studies have shown that BCR‐ABL1 is itself involved in the production of VEGF in CML cells 51, 53, 54. In addition, BCR‐ABL1 has been implicated in the production of histidine decarboxylase (HDC) and thus in the synthesis of histamine in CML cells 68. However, not all angiogenic and fibrogenic cytokines are produced in CML cells in a BCR‐ABL1‐dependent manner.…”

Section: Basophils As Unique Source Of Microenvironment‐remodelling Smentioning

confidence: 99%

The underestimated role of basophils in Ph⁺ chronic myeloid leukaemia

Valent

Horny

Arock

2018

Eur J Clin Investigation

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Chronic myeloid leukaemia (CML) is a hematopoietic neoplasm defined by the chromosome translocation t(9;22) and the related oncogene, BCR‐ABL1. In most patients, leukaemic cells can be kept under control using BCR‐ABL1‐targeting drugs. However, many patients relapse which remains a clinical challenge. In particular, patients with advanced (accelerated or blast phase) CML have a poor prognosis. So far, little is known about molecular and cellular interactions and features that contribute to disease progression and drug resistance in CML. One key prognostic factor at diagnosis is marked basophilia. However, although basophils are well‐known multifunctional effector cells, their impact in CML remains uncertain. In this article, we discuss the potential role of basophils as active contributors to disease evolution and progression in CML. In particular, basophils serve as a unique source of inflammatory, angiogenic and fibrogenic molecules, such as vascular endothelial growth factor or hepatocyte growth factor. In addition, basophils provide vasoactive substances, like histamine as well as the cytokine‐degrading enzyme dipeptidyl‐peptidase IV which may promote stem cell mobilization and the extramedullary spread of stem and progenitor cells. Finally, basophils may produce autocrine growth factors for myeloid cells. Understanding the role of basophils in CML evolution and progression may support the development of more effective treatment concepts.

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“…An alternative explanation would be that terfenadine and loratadine act on additional (undiscovered) HR or other molecular targets in neoplastic MC. Likewise, a number of previous and more recent data suggest that certain CYP450 isoenzymes serve as potential targets of terfenadine and loratadine and thus are mediating anti-neoplastic effects of these agents [22,[39][40][41][42][43]. If so, one could speculate that the other HR blockers tested did not interact with such enzymes in the same way or interact only with other CYP450 variants.…”

Section: Discussionmentioning

confidence: 99%

“…We have recently shown that the HR1 antagonists terfenadine and loratadine inhibit the growth of neoplastic basophils in chronic myeloid leukemia (CML) [22]. However, the effects of HR antagonists on growth of neoplastic MC has not been examined so far.…”

Section: Introductionmentioning

confidence: 99%

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H1-receptor antagonists terfenadine and loratadine inhibit spontaneous growth of neoplastic mast cells

Hadzijusufovic

Peter

Gleixner

et al. 2010

Experimental Hematology

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Objective-In mast cell (MC) neoplasms, clinical problems requiring therapy include i) the local aggressive and sometimes devastating growth of MC and ii) mediator-related symptoms. A key mediator of MC responsible for clinical symptoms is histamine. Therefore, the use of histamine receptor (HR) antagonists is an established approach to block histamine effects in these patients.Methods and Results-We screened for additional beneficial effects of HR antagonists and asked whether any of these agents would also exert growth-inhibitory effects on primary neoplastic MC, the human MC line HMC-1, and on two canine MC lines, C2 and NI-1. We found that the HR1 antagonists terfenadine and loratadine suppress spontaneous growth of HMC-1, C2, and NI-1 cells, as well as growth of primary neoplastic MC in all donors tested (human patients, n=5; canine patients, n=8). The effects of both drugs were found to be dose-dependent (IC 50 : terfenadine, 1-20 μM; loratadine, 10-50 μM). Both agents also produced apoptosis in neoplastic MC and augmented apoptosis-inducing effects of two KIT-targeting drugs, PKC412 and dasatinib. The other HR1 antagonists (fexofenadine, diphenhydramine) and HR2 antagonists (famotidine, cimetidine, ranitidine) tested did not exert substantial growth-inhibitory effects on neoplastic MC. None of the histamine receptor blockers were found to modulate cell cycle progression in neoplastic MC. Conclusions-The Europe PMC Funders Group Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts (terfenadine) alone or in combination with KIT-inhibitors, can also affect in vivo neoplastic MC growth remains to be determined.

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The CML-related oncoprotein BCR/ABL induces expression of histidine decarboxylase (HDC) and the synthesis of histamine in leukemic cells

Cited by 22 publications

References 53 publications

Interleukin-17A activation on bronchial epithelium and basophils: a novel inflammatory mechanism

Interleukin-17A activation on bronchial epithelium and basophils: a novel inflammatory mechanism

The underestimated role of basophils in Ph⁺ chronic myeloid leukaemia

H1-receptor antagonists terfenadine and loratadine inhibit spontaneous growth of neoplastic mast cells

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The CML-related oncoprotein BCR/ABL induces expression of histidine decarboxylase (HDC) and the synthesis of histamine in leukemic cells

Cited by 22 publications

References 53 publications

Interleukin-17A activation on bronchial epithelium and basophils: a novel inflammatory mechanism

Interleukin-17A activation on bronchial epithelium and basophils: a novel inflammatory mechanism

The underestimated role of basophils in Ph+ chronic myeloid leukaemia

H1-receptor antagonists terfenadine and loratadine inhibit spontaneous growth of neoplastic mast cells

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The underestimated role of basophils in Ph⁺ chronic myeloid leukaemia