Mechanisms accounting for the defective natural killer activity in patients with hairy cell leukemia

Trentin, Luca; Zambello, Renato; Agostini, C.; Ambrosetti, Achille; Chisesi, Teodoro; Raimondi, Roberto; Bulian, Pietro; Pizzolo, Giovanni; Semenzato, Gianpietro

doi:10.1182/blood.v75.7.1525.bloodjournal7571525

Cited by 3 publications

(7 citation statements)

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“…Thus low pretreatment NK activity may increase with interferon although not always to normal levels. NK-cell numbers may increase if they were low before treatment but in leukaemic patients with high NK-cell counts the numbers decline with interferon treatment (Grvfiths & Cawley, 1987, Foon et al 1986, Semenzato et al 1986). The response to IFN appears slowly over several months.…”

Section: Discussionmentioning

confidence: 99%

“…Studies on the nature of the defective NK function in HCL have suggested that the capacity to bind to target cells is reduced, but more particularly that killing of bound targets is impaired (Fontana et al 1986, Trentin et al 1990, and this may be associated with reduced production of NK cytotoxic factor (Trentin et al 1990). These results were interpreted as functional immaturity of the NK cells and this is also implied by our finding of reduced responsiveness to interferon in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…Severe infections are a major problem in these patients (Golomb & Haddad 1984). Treatment includes splenectomy (Van Norman et al 1986) and interferon alpha (Quesadu et al 1984).…”

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confidence: 99%

“…The study of NK cells in patients with hairy cell leukaemia is thus of interest both in connection with the pathophysiology of the disease (Fontuna et al 1986;Foa et al 1986) and the response to interferon treatment (Semenzato et al 1986;Gastl et al 1986;Grgfiths & Cawley 1987). Such studies have revealed that NK-cell activity is often depressed in patients with HCL.…”

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confidence: 99%

“…Such studies have revealed that NK-cell activity is often depressed in patients with HCL. In contrast, NK-cell numbers have been found to be normal or high (Semenzato et al 1986;Fontana et al 1986;Foa et al 1986), although some workers have reported a decrease in the number of NK cells (Gastl et al 1986;Grijjfiths & Cawley 1987). The defect in NK-cell function has been attributed to functional immaturity of NK cells (Fontana et al 1986) or dilution by hairy cells (Grijjfiths & Cawley 1987).…”

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confidence: 99%

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Natural killer cell function and malignant cell phenotype in hairy cell leukaemia

Ögmundsdóttir

Thorsteinsson

Sigfússon

et al. 1992

APMIS

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0. Natural killer cell function and malignant cell phenotype in hairy cell leukaemia. APMIS 100: 10-20, 1992.We have followed for 33 months the changes that occurred in natural killer (NK) cell numbers and activity in a patient (A) with hairy cell leukaemia (HCL), using a single cell assay and a microcytotoxicity assay. The composition of the peripheral blood mononuclear cell population and malignant cell phenotype were also analysed. During this period he received treatment with interferon and his grossly enlarged spleen was removed. Four further patients were also studied, two were splenectomized and all had received treatment with interferon. In four of the five patients studied there was an apparent link between low NK activity and presence of a tumour-infiltrated spleen, and in the fifth patient, who was aleukemic and had no splenomegaly, NK function was related to disease activity. There was no correlation between NK activity and the number of target binding (TB) cells in these five patients. IFN had little direct effect on overall NK activity, but the proportion of killing cells among TB cells was increased. Three patients showed binding of several cells to a single target. Further analysis revealed that in the patients most of the TB cells were not CD56-positive NK cells, in contrast to TB cells from normal subjects. In patient A a large proportion (84%) of TB cells were identified as malignant cells and in patient E 15% of TB cells were malignant cells. The phenotype of the malignant cells was: CD19 + ,HLA-DR + and CD25(Tac) + ,except for patient A. In this patient the hairy cells were positive for the NK marker CD56 as well as the monocyte marker CD14. Furthermore, a change occurred in phenotype as only later samples carried CD25. It is concluded that the level of NK function correlates closely with disease activity in HCL and that competitive target cell binding by malignant cells may be one cause of depressed NK-cell function in hairy cell leukaemia.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…Severe infections are a major problem in these patients (Golomb & Haddad 1984). Treatment includes splenectomy (Van Norman et al 1986) and interferon alpha (Quesadu et al 1984).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Natural killer cell function and malignant cell phenotype in hairy cell leukaemia

Ögmundsdóttir

Thorsteinsson

Sigfússon

et al. 1992

APMIS

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Dissection of the bone marrow microenvironment in hairy cell leukaemia identifies prognostic tumour and immune related biomarkers

Koldej

Prabahran

Tan

et al. 2021

Sci Rep

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Hairy cell leukaemia (HCL) is a rare CD20+ B cell malignancy characterised by rare “hairy” B cells and extensive bone marrow (BM) infiltration. Frontline treatment with the purine analogue cladribine (CDA) results in a highly variable response duration. We hypothesised that analysis of the BM tumour microenvironment would identify prognostic biomarkers of response to CDA. HCL BM immunology pre and post CDA treatment and healthy controls were analysed using Digital Spatial Profiling to assess the expression of 57 proteins using an immunology panel. A bioinformatics pipeline was developed to accommodate the more complex experimental design of a spatially resolved study. Treatment with CDA was associated with the reduction in expression of HCL tumour markers (CD20, CD11c) and increased expression of myeloid markers (CD14, CD68, CD66b, ARG1). Expression of HLA-DR, STING, CTLA4, VISTA, OX40L were dysregulated pre- and post-CDA. Duration of response to treatment was associated with greater reduction in tumour burden and infiltration by CD8 T cells into the BM post-CDA. This is the first study to provide a high multiplex analysis of HCL BM microenvironment demonstrating significant immune dysregulation and identify biomarkers of response to CDA. With validation in future studies, prospective application of these biomarkers could allow early identification and increased monitoring in patients at increased relapse risk post CDA.

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Risk of Second Cancer in Patients With Hairy Cell Leukemia: Long-Term Follow-Up

Federico¹

2002

Journal of Clinical Oncology

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Mechanisms accounting for the defective natural killer activity in patients with hairy cell leukemia

Cited by 3 publications

References 0 publications

Natural killer cell function and malignant cell phenotype in hairy cell leukaemia

Natural killer cell function and malignant cell phenotype in hairy cell leukaemia

Dissection of the bone marrow microenvironment in hairy cell leukaemia identifies prognostic tumour and immune related biomarkers

Risk of Second Cancer in Patients With Hairy Cell Leukemia: Long-Term Follow-Up

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