Purine metabolism enzymes and immunological phenotype in chronic B-cell malignancies: chronic lymphocytic leukemia, prolymphocytic leukemia and hairy cell 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.Keywords:
Prolymphocytic leukemia
Chronic leukemia
Hairy Cell
Immunophenotyping
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Aspirates of bone marrow with chronic lymphocytic leukemia, hairy cell leukemia, and Richter's syndrome were stained by the argyrophilic nucleolar organizer region (AgNOR) method and analyzed. The AgNOR configurations of small cells of chronic lymphocytic leukemia, hairy cell leukemia, and lymphosarcoma cells were similar and most often consisted of a single large dot, a single small regular bleb, and two dots of various sizes, similar to patterns of normal lymphocytes. The large cells of chronic lymphocytic leukemia and prolymphocytic leukemia cells transformed from chronic lymphocytic leukemia contained larger AgNORs (group II), that is patterns consistent with proliferation. Richter's syndrome lymphoma cells contained even larger AgNORs. A single large regular bleb, small regular bleb and large irregular bleb were most common. Cells with only small structures were very rare.
Bleb (medicine)
Prolymphocytic leukemia
Hairy Cell
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Abstract We report a case with mixed features of hairy cell leukemia (HCL) and chronic lymphocytic leukemia (CLL), which may represent a hybrid form of these two entities. Hairy projections were demonstrated on leukemic cells in the peripheral blood. Surface marker studies of blood and spleen specimens by flow cytometry and immunohistochemistry showed immunophenotype characteristic of HCL, namely, monoclonal IgG‐kappa, positive reactions to CD 11c, CD 19, CD 20, CD 22, and HLA‐DR, but negative reactions to CD 3, CD 5, CD 7 and CD 10. The only atypical finding was the absence of CD 25. Immunogenotyping showed rearrangement of heavy‐chain and kappa light chain genes. Leukemic cells were also positive for tartrate‐resistant acid phosphatase (TRAP). A pseudosinus pattern was demonstrated in the spleen. However, the leukemic cells in the spleen showed atypical cytologic features. Clinically, the patient had generalized lymphadenopathy, high leukocyte counts, Coombs' negative hemolysis, hypoimmunoglobulinemia and IgG‐kappa monoclonal gammopathy, features more consistent with CLL than HCL. Although only CD 11c, CD 22, CD 25 and TRAP are characteristic for HLC and CD 5, characteristic for CLL, a panel of eight markers is recommended for the differential diagnosis of HCL, CLL and other low‐grade B‐cell neoplasms, which may share some common features, making a clear‐cut diagnosis difficult.
Immunophenotyping
Hairy Cell
Chronic 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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The French-American-British group's proposal for the classification of chronic lymphoid leukemias is unique at this time. Testing, expanding, and adding to the theory by immunophenotyping will help to additionally characterize this group of diseases.Peripheral blood samples from 242 patients with chronic lymphoid leukemias were analyzed for immunologic evaluation of the following subtypes: typical chronic lymphocytic leukemia (CLL), 189; CLL with pleomorphic lymphocytes (CLL-pleo), 19; CLL of mixed cell type (CLL/PL), 20; prolymphocytic leukemia (PLL), 22; hairy cell leukemia (HCL), 10; HCL-variant, 1; and splenic lymphoma with villous lymphocytes, 1.The phenotype of CLL and CLL-pleo was weak surface immunoglobulin (SIg) with positive results of mouse rosettes (MR+), CD5+, and CD22-. Of PLL and HCL, it was strong SIg, MR-, CD5-, and CD22+. By analyzing the four markers and accepting the relevant results of two or more as sufficient for diagnosis, all cases (100%) of CLL, CLL-pleo, PLL, and HCL were diagnosed. CLL/PL showed the phenotype of CLL in 66.67% and of PLL in 33.33% of patients. The frequency of cases with weak fluorescence in decreasing order was CLL, CLL-pleo, CLL/PL, and PLL and HCL. The same sequence applied to the mean percentage of mouse rosette-forming cells and CD5 cells, but the sequence was reversed for CD22 cells.SIg intensity, MR, CD5, and CD22 constitute the minimum number of immune markers for the differential diagnosis of the subtypes of chronic lymphoid leukemia. The frequency of the four markers among the subtypes suggested that CLL and CLL-pleo have identical phenotypes and that the five subtypes follow a continuous range of B-cell differentiation from early mature (CLL and CLL-pleo) to late mature pre-plasma cell stages (PLL followed by HCL), with CLL/PL of intermediate maturity.
Immunophenotyping
CD5
Prolymphocytic leukemia
Chronic leukemia
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CD5
Prolymphocytic leukemia
Immunophenotyping
Chronic leukemia
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Introduction 1123 Chronic lymphocytic leukemia 1123 Epidemiology 1124 Diagnosis 1124 Clinical features 1124 Clinical staging and prognostic markers 1125 Clinical staging systems 1125 Traditional prognostic markers 1125 New prognostic markers 1126 Treatment 1127 Pretreatment evaluation 1127 Criteria for response and minimal residual disease 1128 First-line therapy 1129 Treatment at relapse 1132 Stem cell transplantation 1134 New therapies 1135Richter large cell transformation 1135 Management of complications 1136 B cell prolymphocytic leukemia 1137 Immunophenotype and cytogenetics 1137 Clinical course and management 1137 Hairy cell leukemia 1137 Morphology and immunophenotype 1138 Treatment 1138 Splenectomy 1138 Interferon alpha 1138 Pentostatin 1138 Cladribine 1138 Treatment at relapse 1138 Hairy cell leukemia variant 1139 Key points 1139 References 1140Small B cell lymphoproliferative disorders comprise a variety of disease entities, the commonest of which is chronic lymphocytic leukemia (CLL). Rarer primary B cell leukemias include B prolymphocytic leukemia (PLL) and hairy cell leukemia (HCL). In addition, clonal B cells may appear in the peripheral blood originating from a primary non-Hodgkin lymphoma (NHL).
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Prolymphocytic leukemia
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Mononuclear cells concentrated from 11 patients with chronic lymphocytic leukemia (CLL), 7 with non-Hodgkin's lymphoma in leukemic phase (NHL), 5 with hairy cell leukemia (HCL), 1 with prolymphocytic leukemia (PLL), and 1 with plasma cell leukemia (PCL) were induced to differentiate with various doses of TPA. The degree of induction was followed for up to 6 days by measuring the expression of surface membrane markers (SmIg and GP-70) and Ig secretion, the induction of tartrate-resistant acid phosphatase (TRAP) and by recording ultrastructural changes as seen by electronmicroscopy. The results show a dose and time dependency of the TPA effect and a great heterogeneity in the cellular response, particularly in cells obtained from B-CLL patients. TPA induced two main features, namely the development of "plasmacytoid" or "hairy cell" leukemia features that clearly depended on the dose and duration of treatment with the phorbol ester. The plasmacytoid features were more frequently encountered with lower doses (1 ng/ml) of TPA and were more evident after shorter exposures to TPA (1-2 days). Nevertheless, the hairy cell features were more striking after incubation with higher concentrations of TPA (10-100 ng/ml) after longer periods of incubation (up to 6 days) with lower doses of TPA. The various features of differentiation measured including cell morphology, surface membrane markers, Ig secretion, and TRAP staining, were frequently independent of each other, suggesting an autonomous pathway of differentiation for some of these features. Furthermore, in most of the cases, hairy cell leukemia features were obtained more frequently following TPA exposure than plasmacytic changes.
Hairy Cell
Plasma cell leukemia
Prolymphocytic leukemia
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Objective To investigate the characteristic immunophenotype of B cell chronic lymphoid leukemia in china. Method Single and multiparameter flow cytometry were used to analysis 163 cases of B cell chronic lymphoid leukemia. Results 71.8%(117/163) of cases co-expressed CD5 and B cell markers. The patients were classified into category of B cell chronic lymphocytic leukemia(B-CLL), hairy cell leukemia(HCL) and other B-cell lymphoproliferative disorders(LPDs) by using the scoring system that was recommended by world health organization (WHO). The B-CLL typically display the composite phenotypes: CD5+,CD23+,CD20+,CD19+,HLA-DR+,but the CD22,CD11c,CD25 and FMC7 were variable present in some B-CLL cases.CD103 seems the most specific marker for HCL.To differentiate diagnosis of atypical B-CLL with B-prolymphocytic leukemia(B-PLL) or mantle cell lymphoma(MCL), one must not rely exclusively on immunophenotypic dates, cytogenetic or molecular biology detection would be helpful. The index of froward scatter( FSC) and antigens expression of tumor B cells could be calculated by dividing the relevant value of residual normal T cell within same sample as internal control, so the cell size and the intensity of antigen expression could be comparable each other and quantitative between different investigations. Conclusion immunophenotypic analysis is an extremely useful adjunct in the diagnosis of chronic lymphoid leukemia.
Prolymphocytic leukemia
Immunophenotyping
CD5
Chronic leukemia
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The chronic lymphoid leukemias are a heterogeneous group of disorders with different immunologic, biologic, and clinical features. The most common of these are the B-cell diseases, chronic lymphocytic leukemia and its variants, including prolymphocytic leukemia and hairy cell leukemia. The increased use of immunophenotyping has identified a number of other less common but related disorders. Despite being clonal disorders, the chronic B-cell leukemias exhibit immunologic abnormalities in multiple other lineages, the mechanism for which is not clear. Fludarabine, 2'-deoxycoformycin, and 2-chlorodeoxyadenosine are purine analogues that have advanced the treatment of chronic B-cell leukemias. Fludarabine appears to be the single most effective agent for chronic lymphocytic leukemia, while 2'-deoxycoformycin and 2-chlorodeoxyadenosine are both extremely effective in hairy cell leukemia. A recently completed comparison of α-interferon with 2'-deoxycoformycin in hairy cell leukemia may redefine the standard therapy for this disorder. Continued interaction between laboratory and clinical scientists is essential for continued progress in these diseases.
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