scholarly journals Increased density of ecto 5' nucleotidase antigen on leukemic T cells from patients with cutaneous T-cell lymphoma and adult T-cell leukemia/lymphoma

Blood ◽  
1989 ◽  
Vol 74 (7) ◽  
pp. 2486-2492 ◽  
Author(s):  
Y Fukunaga ◽  
SS Evans ◽  
M Yamamoto ◽  
Y Ueda ◽  
K Tamura ◽  
...  

Abstract Malignant CD4+ T cells in adult T-cell leukemia/lymphoma (ATL) and cutaneous T-cell lymphoma (CTCL) express a number of cell surface molecules that are upregulated on normal T cells activated by foreign antigen. In this report we describe an interesting exception to the parallel phenotypic features of activated T cells and malignant CD4+ T cells. A monoclonal antibody (MoAb; termed 27.2) that was raised to HTLV-1+, CD4+25+ leukemic T cells stained weakly 25% of peripheral T cells, including approximately 50% of CD8+ T cells and 20% of CD4+ T cells. Flow cytometry analysis indicated that the surface density of the 27.2 antigen was unchanged or diminished when normal T cells were activated by antigen. However, 3/4 Sezary cases and 4/8 cases of ATL had relatively high densities of the 27.2 antigen. Immunoprecipitation and sodium dodecylsulfate polyacrylamide gel electrophoresis of the NP- 40-solubilized membranes of surface-iodinated ATL cells indicated that MoAb 27.2 reacted with a 75 Kd molecule. The size and distribution of the 27.2 antigen on T cell subsets suggested that it might be the enzyme ecto-5′ nucleotidase (NT), a phosphatidylinositol-linked enzyme that catalyzes dephosphorylation of monophosphate nucleotides to their respective nucleosides. This was confirmed by demonstrating that lymphocyte ecto-5′NT activity was blocked partially and inhibited completely by preincubating cells with MoAb 27.2 for 1 hour at 4 degrees C and 24 hours at 37 degrees C, respectively. When used with a second MoAb (27.1) to a novel T cell activation antigen found on all CTCL and ATL leukemias examined, 27.2 was found to discriminate between normal and leukemic T cells in two patients with ATL. These studies suggest that ecto-5′NT has diagnostic value in T cell malignancies and may be aberrantly expressed in some cases of ATL and CTCL.

Blood ◽  
1989 ◽  
Vol 74 (7) ◽  
pp. 2486-2492
Author(s):  
Y Fukunaga ◽  
SS Evans ◽  
M Yamamoto ◽  
Y Ueda ◽  
K Tamura ◽  
...  

Malignant CD4+ T cells in adult T-cell leukemia/lymphoma (ATL) and cutaneous T-cell lymphoma (CTCL) express a number of cell surface molecules that are upregulated on normal T cells activated by foreign antigen. In this report we describe an interesting exception to the parallel phenotypic features of activated T cells and malignant CD4+ T cells. A monoclonal antibody (MoAb; termed 27.2) that was raised to HTLV-1+, CD4+25+ leukemic T cells stained weakly 25% of peripheral T cells, including approximately 50% of CD8+ T cells and 20% of CD4+ T cells. Flow cytometry analysis indicated that the surface density of the 27.2 antigen was unchanged or diminished when normal T cells were activated by antigen. However, 3/4 Sezary cases and 4/8 cases of ATL had relatively high densities of the 27.2 antigen. Immunoprecipitation and sodium dodecylsulfate polyacrylamide gel electrophoresis of the NP- 40-solubilized membranes of surface-iodinated ATL cells indicated that MoAb 27.2 reacted with a 75 Kd molecule. The size and distribution of the 27.2 antigen on T cell subsets suggested that it might be the enzyme ecto-5′ nucleotidase (NT), a phosphatidylinositol-linked enzyme that catalyzes dephosphorylation of monophosphate nucleotides to their respective nucleosides. This was confirmed by demonstrating that lymphocyte ecto-5′NT activity was blocked partially and inhibited completely by preincubating cells with MoAb 27.2 for 1 hour at 4 degrees C and 24 hours at 37 degrees C, respectively. When used with a second MoAb (27.1) to a novel T cell activation antigen found on all CTCL and ATL leukemias examined, 27.2 was found to discriminate between normal and leukemic T cells in two patients with ATL. These studies suggest that ecto-5′NT has diagnostic value in T cell malignancies and may be aberrantly expressed in some cases of ATL and CTCL.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christine L. Jones ◽  
◽  
Andrea Degasperi ◽  
Vieri Grandi ◽  
Tauanne D. Amarante ◽  
...  

AbstractT-cell non-Hodgkin’s lymphomas develop following transformation of tissue resident T-cells. We performed a meta-analysis of whole exome sequencing data from 403 patients with eight subtypes of T-cell non-Hodgkin’s lymphoma to identify mutational signatures and associated recurrent gene mutations. Signature 1, indicative of age-related deamination, was prevalent across all T-cell lymphomas, reflecting the derivation of these malignancies from memory T-cells. Adult T-cell leukemia-lymphoma was specifically associated with signature 17, which was found to correlate with the IRF4 K59R mutation that is exclusive to Adult T-cell leukemia-lymphoma. Signature 7, implicating UV exposure was uniquely identified in cutaneous T-cell lymphoma (CTCL), contributing 52% of the mutational burden in mycosis fungoides and 23% in Sezary syndrome. Importantly this UV signature was observed in CD4 + T-cells isolated from the blood of Sezary syndrome patients suggesting extensive re-circulation of these T-cells through skin and blood. Analysis of non-Hodgkin’s T-cell lymphoma cases submitted to the national 100,000 WGS project confirmed that signature 7 was only identified in CTCL strongly implicating UV radiation in the pathogenesis of cutaneous T-cell lymphoma.


2006 ◽  
Vol 45 (4) ◽  
pp. 447-449 ◽  
Author(s):  
F. H. Sakamoto ◽  
G. W. B Colleoni ◽  
S. P. Teixeira ◽  
M. Yamamoto ◽  
N. S. Michalany ◽  
...  

2021 ◽  
Author(s):  
Garry Nolan ◽  
Darci Phillips ◽  
Magdalena Matusiak ◽  
Belén Gutierrez ◽  
Salil Bhate ◽  
...  

Abstract Anti-PD-1 immunotherapies have transformed cancer treatment, yet the determinants of clinical response are largely unknown. We performed CODEX multiplexed tissue imaging and RNA sequencing on 70 tumor regions from 14 advanced cutaneous T cell lymphoma (CTCL) patients enrolled in a clinical trial of pembrolizumab therapy. Clinical response was not associated with the frequency of tumor-infiltrating T cell subsets, but rather with striking differences in the spatial organization and functional immune state of the tumor microenvironment (TME). After treatment, pembrolizumab responders had a localized enrichment of tumor and CD4+ T cells, which coincided with immune activation and cytotoxic PD-1+ CD4+ T cells. In contrast, non-responders had a localized enrichment of Tregs pre- and post-treatment, consistent with a persistently immunosuppressed TME and exhausted PD-1+ CD4+ T cells. Integrating these findings by computing the physical distances between PD-1+ CD4+ T cells, tumor cells, and Tregs revealed a spatial biomarker predictive of pembrolizumab response. Finally, the chemokine CXCL13 was upregulated in tumor cells in responders post-treatment, suggesting that chemoattraction of PD-1+ CD4+ T cells towards tumor cells facilitates a positive outcome. Together, these data show that T cell topography reflects the balance of effector and suppressive activity within the TME and predicts clinical response to PD-1 blockade in CTCL.


1991 ◽  
Vol 2 (3) ◽  
pp. 229
Author(s):  
Tetsuo Nagatani ◽  
Toshiko Matsuzaki ◽  
Naoko Baba ◽  
Hideaki Miyamoto ◽  
Hiroshi Nakajima

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Min Soo Jang ◽  
Dong Young Kang ◽  
Jong Bin Park ◽  
Sang Tae Kim ◽  
Kee Suck Suh

Cutaneous T-cell lymphoma describes a heterogeneous group of neoplasms of skin homing T cells that vary considerably in clinical presentation, histologic appearance, immunophenotype, and prognosis. This paper addresses the cutaneous T-cell lymphoma in Asians with respect to clinical-epidemiologic and histopathological features. Compared with Western countries, Asia usually has higher rates of cutaneous T-cell lymphomas such as extranodal NK/T-cell lymphoma, hydroa vacciniforme-like lymphoma, subcutaneous panniculitis T-cell lymphoma, and adult T-cell leukemia/lymphoma and lower rates of cutaneous B-cell lymphomas. Among many variants of mycosis fungoides, hypopigmented lesions, pityriasis lichenoides-like lesions, and ichthyosiform lesions are more prevalent in Asia than in the West. Adult T-cell leukemia/lymphoma is endemic in southwestern Japan especially in the Kyushu island. The clinicopathologic characteristics of cutaneous lymphoma vary according to geography, and this may be ascribed to genetic and environmental etiologic factors.


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