[Chronic lymphocytic leukemia and hairy cell leukemia].
0
Citation
0
Reference
10
Related Paper
Cite
In recent years, major advances in our understanding of the biology of the chronic lymphoid leukemias have been accompanied by the emergence of new therapeutic options. Chronic lymphocytic leukemia, the most common of these disorders, appears to be related to a failure of apoptosis, leading to accumulation of functionally abnormal lymphocytes. Fludarabine, a nucleoside analogue that may activate apoptosis, has emerged as the most effective agent for newly diagnosed as well as relapsed patients with chronic lymphocytic leukemia. Nevertheless, few if any patients are cured with this agent. Unique chemotherapeutic and biologic therapies are being explored, and new strategies combining several approaches will likely be established. For patients with hairy-cell leukemia, pentostatin and 2-chlorodeoxyadenosine achieve durable complete remissions in 65% to 85% of patients, with comparable toxicity.
Pentostatin
Cladribine
Lymphoid leukemia
Cite
Citations (11)
Leukemic B-cell chronic lymphoproliferative disorders (B-CLPD) are a relatively heterogeneous group of diseases, all of which exhibit a clonal expansion of mature-appearing B-lymphoid cells in the peripheral blood (PB). Both primary leukemias and the leukemic phase of primary lymphomas are included in this category (1). Among the primary B-cell leukemias, chronic lymphocytic leukemia (CLL), prolymphocytic leukemia (PLL), and hairy cell leukemia (HCL) are usually considered; within the primary lymphomas, follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone splenic lymphoma (MZSL), lymphoplasmacytic lymphoma (LPL), and the large B-cell lymphomas (LCLs) exhibit PB involvement more frequently (1).
Prolymphocytic leukemia
Lymphoplasmacytic Lymphoma
Lymphoproliferative Disorders
Follicular lymphoma
Mantle zone
Cite
Citations (11)
The BRAF-V600E mutation defines genetically hairy cell leukemia among B-cell leukemias and lymphomas. In solid tumors, BRAF-V600E is known to aberrantly activate the oncogenic MEK-ERK pathway, and targeted BRAF and/or MEK inhibitors have shown remarkable efficacy in clinical trials in melanoma patients. However, the MEK-ERK pathway status in hairy cell leukemia has not been thoroughly investigated. We assessed phospho-ERK expression in 37 patients with hairy cell leukemia and 44 patients with neoplasms mimicking hairy cell leukemia (40 splenic marginal zone lymphoma, 2 hairy cell leukemia-variant and 2 splenic lymphoma/leukemia unclassifiable) using immunohistochemistry on routine biopsies and/or Western blotting on purified leukemic cells, and correlated the phospho-ERK status with the BRAF-V600E mutation status. Besides confirming the constant presence of BRAF-V600E in all patients with hairy cell leukemia, we observed ubiquitous phospho-ERK expression in this malignancy. Conversely, all 44 cases with neoplasms mimicking hairy cell leukemia were devoid of BRAF-V600E and none expressed phospho-ERK. Furthermore, the two exceptionally rare cases of non-hairy cell leukemia unclassifiable chronic B-cell neoplasms previously reported to be BRAF-V600E+ on allele-specific polymerase chain reaction lacked phospho-ERK expression as well, suggesting the presence of the mutation in only a small part of the leukemic clone in these cases. In conclusion, our findings support the use of phospho-ERK immunohistochemistry in the differential diagnosis between hairy cell leukemia and its mimics, and establish the MEK-ERK pathway as a rational therapeutic target in this malignancy.
Cite
Citations (86)
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
Cite
Citations (2)
Hairy Cell
Malignant Transformation
Cite
Citations (30)
Cellular proteins from malignant cells of the leukemic phase of hairy cell leukemia and other lymphoproliferative diseases characterized by immunological markers were evaluated by sodium dodecyl sulfate gradient-polyacrylamide gel electrophoresis. The protein patterns from eight patients with hairy cell leukemia were essentially identical. The protein patterns from eight patients with chronic lymphocytic leukemia, seven patients with acute lymphocytic leukemia, and four patients with poorly differentiated lymphocytic lymphoma were examined and did not demonstrate a consistent pattern within each disease. The protein patterns of one patient each with T-cell malignant lymphoma, lymphoblastic lymphoma, or acute monocytic leukemia were also examined. The protein pattern for hairy cell leukemia is distinctly different from that of all the other diseases studied; differences were distinct even within and between immunological subtypes.
Acute lymphocytic leukemia
Lymphoproliferative Disorders
Cite
Citations (4)
The authors report two cases of malignant melanoma associated with hairy cell leukemia. Skin neoplasia preceded hematological malignancy in the first observation. Among reports concerning the association of malignant melanoma with hematological diseases, chronic lymphocytic leukemia, Hodgkin's lymphoma and non Hodgkin's lymphoma are preponderant. Epidemiological studies would be of value to predict the expected risk of malignant melanoma in hairy cell leukemia.
Malignant lymphoma
Cite
Citations (0)
Chronic leukemia
Cite
Citations (1)
A consistent stimulus to increase interest in malignant disease is the discovery of new successful treatments. The dramatic activity of the nucleoside analogues, 2'-deoxycoformycin, fludarabine, and 2-chlorodeoxyadenosine, in indolent lymphoproliferative diseases has caused a reawakening of interest in the biology and treatment of chronic lymphocytic leukemia and hairy-cell leukemia. The high response rate has led to a reevaluation of criteria for response in these diseases as well as indications for treatment and prognostic factors.
Cladribine
Deoxycoformycin
Pentostatin
Lymphoproliferative Disorders
Vidarabine
Cite
Citations (3)
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.
Cite
Citations (6)