Deficiency of Lymphocyte Lectin-Dependent Cytotoxicity in Myelodysplastic Syndromes

Fontana, Luigi; Sanctis, G. De; Rossi, Giulio De; Bottari, V.; Petti, Maria Concetta; Ensoli, Fabrizio; Pasqualetti, D; Mandelli, Franco

doi:10.1159/000205269

Cited by 3 publications

(4 citation statements)

References 14 publications

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“…high‐grade MDS, AML or accelerated phase/blast crisis CML) have lower zeta chain expression, although there are clear exceptions. These findings are consistent with reported functional studies ( Fontana et al , 1989 ; Verfaillie et al , 1990 ; Ogata et al , 1995 ; Hamblin, 1992). The significance of abnormal levels in patients with early disease, and the converse, i.e.…”

Section: Discussionsupporting

confidence: 93%

“…Cell‐mediated immunity is frequently suppressed in patients with myeloid malignancies, being most profound in those with advanced disease. Numerous abnormalities have been described in both T‐cell and NK function ( Stupp et al , 1978 ; Rambotti et al , 1982 ; Chang et al , 1989 ; Verfaillie et al , 1990 ; Rajaram et al , 1990 ; Sorskaar et al , 1986 ; Colombat et al , 1988 ; Fontana et al , 1989 ; Hamblin, 1992; Ogata et al , 1995 ). Similar abnormalities are also reported in association with solid tumours, and studies have shown an inherent defect in activation in both NK and T cells from patients with advanced cancer ( Takasugi et al , 1977 ; Whitcomb & Parker, 1977; Miescher et al , 1986 ; Maccubbin et al , 1989 ).…”

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confidence: 99%

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Variable expression of CD3‐zeta and associated protein tyrosine kinases in lymphocytes from patients with myeloid malignancies

et al. 1998

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In myeloid malignancies, T-cell and NK function has been shown to deteriorate with transformation from pre-leukaemia to advanced disease. Immune dysfunction in solid tumours has been attributed to abnormal signal transduction, possibly through altered expression of intracellular components of the TCR/CD3 complex (e.g. CD3-zeta), receptors on NK cells and their associated protein tyrosine kinases (PTKs; p56lck, p59fyn and ZAP-70). Using a flow cytometric method to detect dual-expression of surface proteins and intracellular components of the TCR/CD3 complex, we have studied 46 patients with myeloid malignancies. CD3-zeta expression was abnormal in 64% of patients, and was more prominent in those with advanced disease. Three patients with reduced CD3-zeta were analysed both pre- and post-treatment, and recovery of CD3-zeta expression was associated with successful remission induction (expression of PTKs was variable and reduced levels were seen all disease stages). The results of this study suggest that loss of signalling proteins is not a result of direct contact of leukaemic cells with lymphocytes per se or the extent of the leukaemia burden, but to a specific property of some myeloid malignancies, which is more frequently acquired with greater malignant transformation.

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Section: Discussionsupporting

confidence: 93%

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confidence: 99%

Variable expression of CD3‐zeta and associated protein tyrosine kinases in lymphocytes from patients with myeloid malignancies

et al. 1998

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“…An impairment of lymphocyte cytotoxic activity, mostly involving NK activity, is commonly reported in MDS patients and out previous data demonstrated a progressive reduction of this function from refractory anaemia to refractory anaemia with excess blasts in transformation [9]. This finding may support the infectious recurrences and the growth advantage of neoplastic clones in the development of MDS.…”

Section: References Discussionmentioning

confidence: 53%

“…Nevertheless, the IFNs are also able to improve the immune response by potentiating certain lymphocyte and polymorphonuclear cell functions, such as cytotoxic activities, that play a relevant role in immunosurveillance against infectious and neoplastic agents [14,3,15,27,8]. In the light of our previous studies demonstrating an impairment of cytotoxic functions in MDS patients [9,10], we analysed the in vitro effect of recombinant IFN 7 on cytotoxicity mediated by both lymphoid and polymorphonuclear cells from 16 patients.…”

Section: Introductionmentioning

confidence: 99%

Ability of recombinant interferon γ in vitro to restore the defective polymorphonuclear-cell-but not lymphocyte-mediated cytotoxic activities in patients with myelodysplastic syndromes

Sanctis¹,

Bottari²,

Frezzolini³

et al. 1992

Cancer Immunol Immunother

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In this study we analysed the in vitro effect of recombinant interferon gamma on cytotoxic activities mediated by both lymphoid and polymorphonuclear cells from 16 patients with myelodysplastic syndromes. Our results indicate the inability of interferon to restore the defective natural killer activity, natural killer cells and lectin-induced cytotoxicity. On the contrary we detected a boosting effect on the depressed polymorphonuclear cell cytotoxic activities. In our view, the ability of interferon to potentiate polymorphonuclear cell lytic efficiency could support an alternative defensive pathway against either neoplastic or infectious agents.

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Analysis of bone marrow and peripheral blood immunoregulatory lymphocytes in patients with myelodysplastic syndrome

Iwase¹,

Aizawa²,

Kuriyama³

et al. 1995

Ann Hematol

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The cell surface phenotype of immunoregulatory lymphocytes in bone marrow (BM) and peripheral blood (PB) in myelodysplastic syndrome (MDS), a stem cell disorder, was analyzed. Mononuclear cells from 25 patients with refractory anemia (RA) and nine with RA with an excess of blasts (RAEB) were characterized by two-color flow cytometry using various monoclonal antibodies. No significant change of CD3+, CD4+, and CD8+ cells in PB, but a decrease of the percent of positive cells for CD8++ among the total lymphocyte (%CD8++) was noticed in RA patients. On the other hand, in BM of RA patients, a decrease in the number of CD4+ cells, but not CD8++ cells, was noted. In RAEB patients, the absolute numbers of CD3+, CD4+, CD8+, and CD8++ cells in BM were decreased; however, the ratio of these lymphocytes was not changed. No change was observed among the CD4+ subsets in PB of RA or RAEB patients. In BM, a decrease in percentage of CD4+CD45RA+ (%CD4+CD45RA+; naive cell) and increases in CD4+CD45RO+ (%CD4+CD45RO+; memory cell) and CD4+CD29+ (%CD4+CD29+; helper/inducer) among CD4+ cells were found in both RA and RAEB patients. Analysis of the CD8++ subset showed an increased number of CD8++CD11a+ cells (activated CTL) in both BM and PB of RA patients, but not of RAEB patients. Furthermore, increments in CD56+ and CD16+ cells among CD3- cells (natural killer; NK cells) were seen in RA patients but not in RAEB patients. It remains unclear whether lymphocytes in MDS patients were involved in the abnormal (MDS) clones, but our results regarding the increments of CD8++CD11a+ and NK cells in RA patients suggest that the mechanism of immune surveillance against the abnormal MDS clones was activated in these RA patients, but not in RAEB patients. Further investigation is required to clarify the functions of these immunoregulatory lymphocytes in MDS patients.

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Deficiency of Lymphocyte Lectin-Dependent Cytotoxicity in Myelodysplastic Syndromes

Cited by 3 publications

References 14 publications

Variable expression of CD3‐zeta and associated protein tyrosine kinases in lymphocytes from patients with myeloid malignancies

Variable expression of CD3‐zeta and associated protein tyrosine kinases in lymphocytes from patients with myeloid malignancies

Ability of recombinant interferon γ in vitro to restore the defective polymorphonuclear-cell-but not lymphocyte-mediated cytotoxic activities in patients with myelodysplastic syndromes

Analysis of bone marrow and peripheral blood immunoregulatory lymphocytes in patients with myelodysplastic syndrome

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