Synthesis of a novel cytokine and its gene (LD78) expressions in hematopoietic fresh tumor cells and cell lines.

Yamamura, Yukie; Hattori, Toshio; Obaru, Kenshi; Sakai, Kenji; Asou, Norio; Takatsuki, Kiyoshi; Ohmoto, Yasukazu; Nomiyama, Hisayuki; Shimada, Kaoru

doi:10.1172/jci114353

Cited by 49 publications

(18 citation statements)

References 24 publications

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“…Moreover, several secreted (cytokine) and cell surface-associated (receptor) factors serve as important clues for monitoring the activity and prognosis of patients with ATL/ATLL (Yasuda et al 1988;Yamada et al 1996;Mori and Prager 1998). We have also shown that ATL/ ATLL cells express the chemokine ligand 3 (Yamamura et al 1989). Subsequently, ATL/ATLL cells were found to be CCR4 + , which led to the development of anti-CCR4 monoclonal antibody (MoAb) therapy (KW-0761 or mogamulizumab) after discovering that about 90% of ATL/ATLL samples are positive for CCR4 (Ishida et al 2003).…”

Section: Introductionmentioning

confidence: 60%

Galectin-9 as a Predictive Marker for the Onset of Immune-Related Adverse Effects Associated with Anti-CCR4 MoAb Therapy in Patients with Adult T Cell Leukemia

Mohammed

Chagan-Yasutan

Ashino

et al. 2017

Tohoku J. Exp. Med.

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Adult T-cell leukemia/lymphoma (ATL/ATLL) is one of the most malignant lymphomas with poor prognosis. ATL/ATLL cells express CC chemokine receptor 4, and mogamulizumab (anti-CCR4 monoclonal antibody) exhibits strong cytotoxicity for ATL/ATLL cells. We analyzed plasma samples of 6 patients with ATL/ATLL treated with chemotherapy followed by mogamulizumab therapy (mogatherapy) for changes in the levels of biomarkers in relation to immune-related adverse effects. As treatment is often associated with skin eruptions, we investigated the profiles of inflammatory cytokines, including galectin-9 (Gal-9), which becomes increased in various infectious diseases and allergic patients. Gal-9, soluble interleukin (IL)-2 receptor, tumor necrosis factor-α, and IL-10 levels were increased before chemotherapy, and Gal-9 levels were associated with the sIL-2 receptor, which reflects tumor burden. Inflammatory levels decreased after chemotherapy. After mogatherapy, 5 of 6 patients attained complete remission (CR), whereas 1 patient showed no response (NR) and died. Among 5 patients with CR, the biomarkers remained low during mogatherapy, except for a 3-5-fold increment in Gal-9 (associated with skin eruptions). A skin biopsy showed infiltration by inflammatory cells and Gal-9 synthesis in areas with CD8 cell infiltration. In the patient with NR, increased levels of Gal-9 and the aforementioned biomarkers were noted 3 days after mogatherapy, followed by opportunistic infections resembling immune reconstitution inflammatory syndrome. Therefore, an increased Gal-9 plasma level in ATL/ATLL indicates tumor burden and reflects immune activation by mogatherapy. These findings may indicate that an increase in the Gal-9 level, a novel immune checkpoint molecule, can reflect immune-related adverse effects of various biotherapies.

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Section: Introductionmentioning

confidence: 60%

Galectin-9 as a Predictive Marker for the Onset of Immune-Related Adverse Effects Associated with Anti-CCR4 MoAb Therapy in Patients with Adult T Cell Leukemia

Mohammed

Chagan-Yasutan

Ashino

et al. 2017

Tohoku J. Exp. Med.

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“…Murine MIP-la has already been demonstrated to have inflammatory and chemokinetic properties (11,50). Recently, we found that high levels of LD78 gene transcripts are present in acute nonlymphotic as well as lymphotic leukemic cells; hence, LD78 is also probably involved in the neoplastic transformation of hematopoietic cells (51).…”

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confidence: 88%

Structures of human genes coding for cytokine LD78 and their expression.

Nakao¹,

Nomiyama²,

Shimada³

1990

Mol. Cell. Biol.

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113

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LD78 is a member of a newly identified superfamily of small inducible proteins involved in inflammatory responses, wound healing, and tumorigenesis. Southern blot analysis of the EcoRI-digested human genomic DNAs, using previously isolated LD78 cDNA as a probe, showed that in each individual there are 4.2-and 4.8-kilobase-pair (kb) fragments and that some have an additional 6.5-kb fragment. The 4.2-kb fragment contained genomic DNA sequences corresponding to the LD78 cDNA and was named the LD78a gene. The 4.8-kb fragment contained similar sequences, showing 94% homology to the LD78a gene, and was named the LD78j gene. The LD78a gene was present in a single or a few copies per haploid genome, whereas the copy number of the LD78, gene and of the 6.5-kb fragment hybridizable to LD78 cDNA varied among the samples tested. Treatment of human myeloid cell lines HL-60 and U937 with phorbol 12-myristate 13-acetate (PMA) increased within 2 h cellular levels of the RNA hybridizable to LD78 cDNA. The human glioma cell line U105MG and primary culture of human fibroblasts also expressed the hybridizable RNA in response to PMA. Addition of cycloheximide had no apparent effect on this response in U937 cells and inhibited the response in fibroblasts, whereas it stimulated the response in HL-60 and U1O5MG cells. mRNA phenotyping experiments revealed that the LD78a and LD78I8 genes were both transcribed in PMA-stimulated U937 cells.We formerly isolated a cDNA clone, named pLD78, from a cDNA library constructed on the poly(A)+ RNA of human tonsillar lymphocytes stimulated with phorbol 12-myristate 13-acetate (PMA) and phytohemagglutinin, using a differential screening procedure (33). Sequence analysis of the pLD78 cDNA revealed that it codes for a protein of 92 amino acid residues, including a putative leader sequence. To obtain information on the function of this LD78 protein, we made a computer search of nucleotide and protein sequence data bases and found that it has significant similarity to small inducible mammalian proteins forming a new cytokine superfamily (for reviews, see references 4, 34, and 49). Although the exact functions of the members of this cytokine superfamily are unknown, a monocyte-derived neutrophil chemotactic factor, now called interleukin-8 (IL-8), is one of the best-characterized proteins (21).Among the members of the superfamily, LD78 has 75% sequence similarity with murine macrophage inflammatory protein la (MIP-lot) (10), also called murine L2G25B (20). Accordingly, we presume that LD78 is a human counterpart of murine MIP-la. Murine MIP-la has already been demonstrated to have inflammatory and chemokinetic properties (11,50). Recently, we found that high levels of LD78 gene transcripts are present in acute nonlymphotic as well as lymphotic leukemic cells; hence, LD78 is also probably involved in the neoplastic transformation of hematopoietic cells (51).We have now obtained evidence for at least three different LD78-like genes in the human genome. Among them, we isolated and characterized two highly ho...

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“…Similarly, as mentioned above, SCI/MIP-lI mRNA is super-induced during endotoxin (lipopolysacharride, LPS) stimulation of murine macrophages (Davatelis et al, 1988), and is super-induced in human T-cell lines by phorbol esters (PMA) and/or PHA and cyclohexamide (Obaru et al, 1986;Yamamura et al, 1989;Blum et al, 1990). Interestingly, a basal level of SCI/MIP-lac mRNA is detected in unstimulated cultured murine macrophage Davatelis et al, 1988) and mast cell lines (Gordon et al, 1990, and M.P. unpublished results), whereas it is undetectable in unstimulated human monocyte (U937) and T-cell (Jurkat) lines although it can be induced by PHA and/or PMA (Obaru et al, 1986;Yamamura et al, 1989;Blum et al, 1990).…”

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confidence: 82%

“…Although it is unlikely that the SCI/MIP-la gene is itself directly involved in the cellular transformation process, nearby genetic lesions which activate proto-oncogenes or inactive suppressor genes may also coincidentally lead to aberrant SCI/MIP-la gene expression. The up-regulation of SCI/MIP-Ia gene expression has been detected in the peripheral blood of a number of ANLL and ALL patients (Yamamura et al, 1989) (Lord & Wright, 1980) and monocytes (Pojda et (Yamamura et al, 1989) and mast cells (Gordon et al, 1990 (Davatelis et al, 1988) and human (Forsdyke, 1985;Obaru et al, 1986;Zipfel et al, 1989) SCI/MIP-lI cDNAs revealed a number of conserved (TATTT) motifs in the 3' untranslated region of the mRNA which have been implicated in the modulation of mRNA stability of a number of other cytokine mRNAs (Caput et al, 1986;Shaw & Kamen, 1986). Similarly, as mentioned above, SCI/MIP-lI mRNA is super-induced during endotoxin (lipopolysacharride, LPS) stimulation of murine macrophages (Davatelis et al, 1988), and is super-induced in human T-cell lines by phorbol esters (PMA) and/or PHA and cyclohexamide (Obaru et al, 1986;Yamamura et al, 1989;Blum et al, 1990).…”

mentioning

confidence: 99%

“…The up-regulation of SCI/MIP-Ia gene expression has been detected in the peripheral blood of a number of ANLL and ALL patients (Yamamura et al, 1989) (Lord & Wright, 1980) and monocytes (Pojda et (Yamamura et al, 1989) and mast cells (Gordon et al, 1990 (Davatelis et al, 1988) and human (Forsdyke, 1985;Obaru et al, 1986;Zipfel et al, 1989) SCI/MIP-lI cDNAs revealed a number of conserved (TATTT) motifs in the 3' untranslated region of the mRNA which have been implicated in the modulation of mRNA stability of a number of other cytokine mRNAs (Caput et al, 1986;Shaw & Kamen, 1986). Similarly, as mentioned above, SCI/MIP-lI mRNA is super-induced during endotoxin (lipopolysacharride, LPS) stimulation of murine macrophages (Davatelis et al, 1988), and is super-induced in human T-cell lines by phorbol esters (PMA) and/or PHA and cyclohexamide (Obaru et al, 1986;Yamamura et al, 1989;Blum et al, 1990). Interestingly, a basal level of SCI/MIP-lac mRNA is detected in unstimulated cultured murine macrophage Davatelis et al, 1988) and mast cell lines (Gordon et al, 1990, and M.P. unpublished results), whereas it is undetectable in unstimulated human monocyte (U937) and T-cell (Jurkat) lines although it can be induced by PHA and/or PMA (Obaru et al, 1986;Yamamura et al, 1989;Blum et al, 1990).…”

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confidence: 99%

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Molecular aspects of a negative regulator of haemopoiesis

Plumb¹,

Graham²,

Grove³

et al. 1991

Br J Cancer

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Synthesis of a novel cytokine and its gene (LD78) expressions in hematopoietic fresh tumor cells and cell lines.

Abstract: Thus, the protein may be involved in the neoplastic transformation of hematopoietic cells.

Cited by 49 publications

References 24 publications

Galectin-9 as a Predictive Marker for the Onset of Immune-Related Adverse Effects Associated with Anti-CCR4 MoAb Therapy in Patients with Adult T Cell Leukemia

Galectin-9 as a Predictive Marker for the Onset of Immune-Related Adverse Effects Associated with Anti-CCR4 MoAb Therapy in Patients with Adult T Cell Leukemia

Structures of human genes coding for cytokine LD78 and their expression.

Molecular aspects of a negative regulator of haemopoiesis

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