scholarly journals Central Role of Protein Kinase Cε in Constitutive Activation of ERK1/2 and Rac1 in the Malignant Cells of Hairy Cell Leukemia

2007 ◽  
Vol 170 (2) ◽  
pp. 745-754 ◽  
Author(s):  
Joseph R. Slupsky ◽  
Aura S. Kamiguti ◽  
Robert J. Harris ◽  
John C. Cawley ◽  
Mirko Zuzel
Keyword(s):  
Protein Kinase ◽  
Hairy Cell Leukemia ◽  
Malignant Cells ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Constitutive Activation

scholarly journals Current role of interferon in hairy cell leukemia therapy: a timely decision

2019 ◽  
Vol 41 (1) ◽  
pp. 88-90 ◽  
Author(s):  
Wellington Fernandes da Silva ◽  
Larissa Lane Cardoso Teixeira ◽  
Vanderson Rocha ◽  
Valeria Buccheri
Keyword(s):  
Hairy Cell Leukemia ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Current Role

Prospective evaluation of internal adenopathy in a cohort of 43 patients with hairy cell leukemia.

1994 ◽  
Vol 12 (2) ◽  
pp. 268-272 ◽  
Author(s):  
D Hakimian ◽  
M S Tallman ◽  
D K Hogan ◽  
A W Rademaker ◽  
E Rose ◽  
...  
Keyword(s):  
Hairy Cell Leukemia ◽  
Disease Duration ◽  
Disease Free Survival ◽  
Newly Diagnosed ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Free Survival ◽  
Median Disease Duration ◽  
Before And After

PURPOSE To determine the role of computed tomography (CT) in patients with hairy cell leukemia (HCL), we report a series of 43 patients prospectively evaluated for internal adenopathy by CT before and after treatment with 2-chlorodeoxyadenosine (2-CdA). PATIENTS AND METHODS CT was performed on 43 consecutive patients with HCL before and 3 months after a single cycle of 2-CdA. Twenty-four patients were previously diagnosed and 19 were newly diagnosed. Adenopathy was considered bulky if the greatest dimension of any confluent mass was between 5 and 10 cm and massive if greater than 10 cm. RESULTS Internal adenopathy was present in six of 43 patients (14%). Three of the six patients had massive abdominal adenopathy and one had bulky abdominal adenopathy. All six patients with adenopathy were previously diagnosed, while none of the 19 newly diagnosed patients had internal adenopathy. In those patients previously diagnosed, the six with adenopathy had a median disease duration of 68 months, while the 18 patients without adenopathy had a median disease duration of 24 months (P = .01). Adenopathy was more common in splenectomized patients. In previously diagnosed patients, adenopathy occurred in five of 10 (50%) splenectomized patients and one of 14 (7%) nonsplenectomized patients (P = .05). However, the 10 splenectomized patients had a median disease duration of 56 months, while the 14 nonsplenectomized patients had a median disease duration of 16 months (P = .004). All six patients had significant reduction in adenopathy 3 months after 2-CdA and were without residual HCL in the bone marrow. CONCLUSION Significant internal adenopathy in patients with HCL is more frequent than previously recognized. Adenopathy is rare at diagnosis and appears to be related to disease duration. As patients treated with 2-CdA have long disease-free survival durations, detection of significant adenopathy by CT scan may be important; however, routine CT scans are not recommended at the time of diagnosis.

scholarly journals Lipopolysaccharide responsiveness of malignant lymphoid cells in a patient with hairy cell leukemia

Blood ◽  
1979 ◽  
Vol 54 (2) ◽  
pp. 524-529 ◽  
Author(s):  
E Tatsumi ◽  
N Domae ◽  
Y Takiuchi ◽  
H Sawada ◽  
S Shirakawa ◽  
...  
Keyword(s):  
Hairy Cell Leukemia ◽  
Mononuclear Cells ◽  
Morphological Changes ◽  
Tritiated Thymidine ◽  
Lymphoid Cells ◽  
Thymidine Uptake ◽  
Malignant Cells ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Peripheral Blood Mononuclear

Abstract The malignant cells in a patient with hairy cell leukemia responded most evidently to lipopolysaccharide (LPS) in in vitro culture for 3 1/2 days when the conventional tritiated thymidine uptake method was used. Since the malignant cells from patients with several other forms of leukemia and the peripheral blood mononuclear cells from healthy individuals did not show a comparable degree of responsiveness to LPS, we could exclude the possibility that this response was due to effects on contaminating normal mononuclear cells or to the nonspecific conditioning effect through LPS-affected contaminating normal monocytes. Morphological changes were observed with photo- and electronmicroscopy. It is likely that the hairy cells from the patient did respond to LPS, and whether or not this phenomenon may be confined to this type of lymphoid leukemia is not being investigated.

The role of autocrine FGF-2 in the distinctive bone marrow fibrosis of hairy-cell leukemia (HCL)

Blood ◽  
2003 ◽  
Vol 102 (3) ◽  
pp. 1051-1056 ◽  
Author(s):  
Khalil A. Aziz ◽  
Kathleen J. Till ◽  
Haijuan Chen ◽  
Joseph R. Slupsky ◽  
Fiona Campbell ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Growth Factor ◽  
Hairy Cell Leukemia ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Cd44 Isoforms ◽  
Hairy Cells

Abstract Bone marrow (BM) fibrosis is a central diagnostic and pathogenetic feature of hairy-cell leukemia (HCL). It is known that fibronectin (FN) produced and assembled by the malignant hairy cells (HCs) themselves is a major component of this fibrosis. It is also known that FN production is greatly enhanced by adhesion of HCs to hyaluronan (HA) via CD44. The aim of the present study was to establish the roles of fibrogenic autocrine cytokines (fibroblast growth factor-2 [FGF-2] and transforming growth factor β [TGFβ]) and of different isoforms of CD44 in this FN production. We show that HC adhesion to HA stimulates FGF-2, but not TGFβ, production and that HCs possess FGF-2 receptor. In a range of experiments, FN production was greatly reduced by blocking FGF-2 but not TGFβ. Moreover FN, but not FGF-2, secretion was blocked by down-regulation of the v3 isoform of CD44 and by addition of heparitinase. These results show that autocrine FGF-2 secreted by HCs is the principal cytokine responsible for FN production by these cells when cultured on HA. The central role of FGF-2 in the pathogenesis of the BM fibrosis of HCL was supported by our immunohistochemical demonstration of large amounts of this cytokine in fibrotic BM but not in HCL spleen where there is no fibrosis. As regards CD44 isoforms, the present work demonstrates that CD44v3 is essential for providing the heparan sulfate necessary for HC stimulation by FGF-2, whereas the signal for production of the cytokine was provided by HA binding to CD44H, the standard hematopoietic form of the molecule.

scholarly journals The role of rituximab in combination with pentostatin or cladribine for the treatment of recurrent/refractory hairy cell leukemia

Cancer ◽  
2007 ◽  
Vol 110 (10) ◽  
pp. 2240-2247 ◽  
Author(s):  
Monica Else ◽  
Nnenna Osuji ◽  
Francesco Forconi ◽  
Claire Dearden ◽  
Ilaria Del Giudice ◽  
...  
Keyword(s):  
Hairy Cell Leukemia ◽  
Hairy Cell ◽  
Cell Leukemia

8 / Role of Novel Agents in Relapsed Hairy Cell Leukemia- A systematic review

2018 ◽  
Author(s):  
Muhammad Sardar ◽  
JEMIN ABY JOSE ◽  
Mohammad Azfar Bilal ◽  
Chaudhry Saad Sohail ◽  
Heyyan Bin Khalil
Keyword(s):  
Systematic Review ◽  
Hairy Cell Leukemia ◽  
Novel Agents ◽  
Hairy Cell ◽  
Cell Leukemia

Molecular Evidence of Ongoing Antigen Driven Somatic Hypermutation in the Natural History of Classic and Variant Hairy Cell Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2648-2648
Author(s):  
Evgeny Arons ◽  
Sarah Davies ◽  
Katherine Still ◽  
Nathan Chai ◽  
Katherine Potocka ◽  
...  
Keyword(s):  
B Cell ◽  
Hairy Cell Leukemia ◽  
Conflicts Of Interest ◽  
Somatic Hypermutation ◽  
Braf V600e ◽  
Molecular Evidence ◽  
Malignant Cells ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Normal Peripheral Blood

Abstract Classic hairy cell leukemia (HCL) is a clonal chronic B-cell malignancy representing 2% of all leukemias, with neoplastic B lymphocytes in the blood, bone marrow and organs of the classic reticuloendothelial system. HCL variant (HCLv) is less common, typically has inferior prognosis, and usually lacks several HCL-related features including BRAF V600E, CD25, and Annexin A1. The malignant cells in HCL and HCLv patients have one or in unusual cases two different functional immunoglobulin heavy chain rearrangements. Significant variability can be observed in the 3rd complementarity determining region (CDR3), comprising the variable heavy (IGHV), diversity (IGHD), and joining (IGHJ) domains. A role for continued antigen selection in the pathogenesis and evolution of HCL and HCLv has been suggested but limited evidence has been found. We examined HCL and HCLv-derived IGHV genes by massive parallel deep sequencing in 15 HCL and 7 HCLv cases. In all studied samples, a productive monoclonal tumor-derived IGH sequence was detected. Analysis of all reads sharing clonal CDR3 motifs revealed the existence of dominant subclone expansion and multiple subclonal variants. Analysis of phylogenetic trees indicated multiple branching and therefore exposure to multiple rounds of somatic hypermutation (SHM) in the evolution of clonally-related malignant cells. To investigate a possible cause of the high SHM activity and the large number of subclones in HCL and HCLv, we studied the expression of activation induced cytidine deaminase (AID), an enzyme essential for somatic hypermutations, expressed by germinal center (GC) B-cells where SHM occurs. In 5 HCL and 3 HCLv cases we detected a high expression level of AID mRNA, including wild-type and 2 splice variants; in 10 HCL, 4 HCLv, and 3 normal peripheral blood samples, AID expression was not detected using standard end-point PCR conditions. However, more sensitive real-time quantitative PCR detected AID transcripts in virtually all tested HCL and HCLv cases, although the range of transcript levels was large between different cases and varied with individual cases over time. The data obtained for both HCL and HCLv fit a model of tumorigenesis in which the BRAF V600E mutation (or another event in HCLv) initiates neoplastic transformation in a GC B-cell committed to terminal differentiation, but still thereafter still targeted by ongoing SHM Disclosures No relevant conflicts of interest to declare.

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