Supplementary Data from Noncanonical Function of AGO2 Augments T-cell Receptor Signaling in T-cell Prolymphocytic Leukemia
Till BraunJohanna StachelscheidNadine BleySebastian OberbeckMoritz OtteTony Andreas MüllerLinus WahnschaffeMarkus GlaßKatharina OmmerMarek FranitzaBirgit GathofJanine AltmüllerMichael HallekDaniel AuguinStefan HüttelmaierAlexandra SchraderMarco Herling
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Supplementary Data from Noncanonical Function of AGO2 Augments T-cell Receptor Signaling in T-cell Prolymphocytic LeukemiaKeywords:
Prolymphocytic leukemia
Prolymphocytic leukemia is an entity characterized by morphologic, immunologic, clinical and behavioral features which allows its keeping apart from chronic lymphoid leukemia. Careful analysis of blood smear is the main step for its diagnosis. Our purpose is to remind this particular chronic lymphoproliferative syndrome which requires energetic initial treatment. Prolymphocytic leukemia de novo as well as a possible transformation of chronic lymphoid leukemia to prolymphocytic leukemia are discussed.
Prolymphocytic leukemia
Chronic leukemia
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Prolymphocytic leukemia
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The chronic lymphocytic leukemia, the prolymphocytic leukemia and the hairy cell leukemia of B-cell immunophenotype are closely related disorders, but differ in their cytomorphological and clinical features. In an attempt to differentiate further among these forms of leukemia some immunological and cytochemical markers were studied. Simultaneously we measured adenosine deaminase and purine nucleosidephosphorylase activities by a method of paper radiochromatography in peripheral blood/bone marrow leukemic cells from 23 patients with chronic lymphocytic leukemia, 5 patients with prolymphocytic leukemia, one with prolymphocytoid transformation of chronic lymphocytic leukemia and 15 patients with hairy cell leukemia. The mosaic of immunological and cytochemical markers based on the sum of positive and negative features allowed for the correct diagnosis in a majority of cases. From the number of 43 investigated cases we found the typical enzyme patterns in 39 of them. On the basis of purine enzyme activity we were able to differentiate between chronic lymphocytic leukemia versus prolymphocytic and hairy cell leukemia. In one patient with chronic lymphocytic leukemia we could detect very early stage of prolymphocytoid transformation by increased activity of purine nucleosidephosphorylase activity. There were only two patients with chronic lymphocytic leukemia who were assigned to the prolymphocytic leukemia on the basis of purine nucleosidephosphorylase activity and two patients with hairy cell leukemia with atypical enzyme pattern attributable to the nonrepresentative number of pathological cells in the peripheral blood. Our study showed that purine nucleosidephosphorylase activity in leukemia cells may be useful as an additional parameter in the distinction of prolymphocytic from lymphocytic leukemia and that it may represent an enzymatic marker for early detection of prolymphocytoid transformation of chronic lymphocytic leukemia. Characteristic purine enzyme pattern was found also for diagnostic confirmation of hairy cell leukemia.
Prolymphocytic leukemia
Chronic leukemia
Hairy Cell
Immunophenotyping
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Prolymphocytic leukemia
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Prolymphocytic leukemia
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Prolymphocytic leukemia
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Background : B-cell prolymphocytic leukemias or T-cell prolymphocytic leukemias are aggressive variants of chronic lymphoid leukemias. The small studies conducted to date have shown median survival durations of approximately 3 years for patients who have B-cell prolymphocytic leukemia and 7.5 months for those who have T-cell prolymphocytic leukemia, compared with about 8 years for patients who have chronic lymphocytic leukemia. In chronic lymphocytic leukemia, chemotherapy consisting of alkylating agents such as cyclophosphamide and chlorambucil combined with prednisone has achieved overall response rates of 50% to 70%, but this regimen has resulted in response rates of less than 25% in prolymphocytic leukemia. Pentostatin (2'-deoxycoformycin; DCF) is a purine analogue that has shown activity in treatment of chronic lymphoid malignancies. Purpose : This prospective phase II trial by the Leukemia Cooperative Group of the European Organization for Research and Treatment of Cancer was performed to assess the activity and toxicity of DCF in prolymphocytic leukemia. Methods : Twenty patients with B-cell or T-cell prolymphocytic leukemia were given DCF at a dosage of 4 mg/m 2 intravenously once a week for 3 weeks, then every other week for three doses. Patients who had at least partial response received maintenance therapy once a month for a maximum of 6 months. Fourteen patients had B-cell prolymphocytic leukemia, and six had T-cell prolymphocytic leukemia, as evidenced by morphologic and immunologic criteria; three were previously untreated, eight had been given one or two chemotherapeutic regimens, and nine had been given more than two. Results : One patient died of an unknown cause during the first 6 weeks of treatment, and one died of disseminated toxoplasmosis during the period of maintenance therapy, 5 months after achieving partial remission. Nine (45% response rate) of the 20 patients achieved partial remission, including seven (50%) of 14 with B-cell prolymphocytic leukemia and two (33%) of six with T-cell prolymphocytic leukemia. The median duration of response was 9 months (range, 2–30 months); for patients with B-cell prolymphocytic leukemia, the median remission duration was 12 months. No complete remission was observed. Toxic effects included nausea and vomiting (30%), infections (30%), and transient increase in liver enzymes (35%) and increatinine (20%) levels. Eight patients experienced thrombocytopenia, the major hematologic toxic effect; four had grade 3 or 4 toxic effects. Conclusion : DCF is active in prolymphocytic leukemia, even as salvage therapy in patients who had received multiple prior chemotherapeutic regimens. Implications : Trials using DCF or other purine analogues alone or in combination with standard chemotherapeutic agents in front-line or salvage therapy are warranted to improve the prognosis of patients with prolymphocytic leukemia. [J Natl Cancer Inst 85:658-662, 1993]
Prolymphocytic leukemia
Pentostatin
Chlorambucil
Deoxycoformycin
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Prolymphocytic leukemia
Abnormality
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The clinical course of a patient with extensive skin involvement due to T-cell prolymphocytic leukemia is described. The malignant cells isolated from the patient's blood and skin were studied utilizing cytochemical analysis and multiple monoclonal antibodies directed against cell surface antigens. The leukemic cells displayed a surface antigen phenotype similar to that of normal post thymic suppressor T-cells. On the basis of this study together with the few published reports, it appears that T-prolymphocytic leukemia is derived from lymphocytes demonstrating either the suppressor or helper phenotype, and that extensive dermal infiltration may be independent of phenotypic classification. Although T-prolymphocytic leukemia shares certain morphologic, cytochemical, and immunologic features with chronic lymphocytic leukemia, it is an aggressive disease with an average survival of approximately 6 months and is best thought of as a distinct pathologic entity. Cancer 52:2049-2054, 1983.
Prolymphocytic leukemia
Infiltration (HVAC)
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