Involvement of CD44-hyaluronan interaction in malignant cell homing and fibronectin synthesis in hairy cell leukemia

Blood ◽  
2000 ◽  
Vol 96 (9) ◽  
pp. 3161-3167 ◽  
Author(s):  
Khalil A. Aziz ◽  
Kathleen J. Till ◽  
Mirko Zuzel ◽  
John C. Cawley

Abstract The tissue homing of malignant hematic cells has both diagnostic and pathogenetic importance. Although such homing is incompletely understood, it generally involves cell adhesion and migration mediated by a number of adhesion receptors and cytokines. In this article, the potential importance of hyaluronan (HA) is examined for the tissue homing of hairy cells (HCs) in hairy cell leukemia (HCL). It is shown that HCs readily adhere to, and spontaneously move on, HA-coated surfaces using CD44. This indicates that activated CD44 and spontaneous movement on HA form part of the intrinsically activated phenotype of HCs. Interleukin-8 (IL-8) inhibited HC movement on HA, and this cell arrest was accompanied by increased actin polymerization and a more pronounced association of CD44 with the cytoskeleton. All of these findings are in sharp contrast to our previous observations with chronic lymphocytic leukemia cells, which are nonmotile on HA, but in response to IL-8 become polarized and motile using the receptor for HA-mediated motility rather than their apparently inactive CD44. Immunohistochemical examination of HCL tissues showed the ubiquitous presence of IL-8 and the prominence of HA in bone marrow stroma and hepatic portal tracts. This suggests that CD44-HA interactions are important in HC homing to these sites, but not to splenic red pulp or hepatic sinusoids, where HA is largely absent. Moreover, engagement of CD44 on HCs stimulates fibronectin synthesis, an observation that is likely to be relevant to the restriction of fibrosis in the disease to HC-infiltrated areas containing HA.

Blood ◽  
2000 ◽  
Vol 96 (9) ◽  
pp. 3161-3167 ◽  
Author(s):  
Khalil A. Aziz ◽  
Kathleen J. Till ◽  
Mirko Zuzel ◽  
John C. Cawley

The tissue homing of malignant hematic cells has both diagnostic and pathogenetic importance. Although such homing is incompletely understood, it generally involves cell adhesion and migration mediated by a number of adhesion receptors and cytokines. In this article, the potential importance of hyaluronan (HA) is examined for the tissue homing of hairy cells (HCs) in hairy cell leukemia (HCL). It is shown that HCs readily adhere to, and spontaneously move on, HA-coated surfaces using CD44. This indicates that activated CD44 and spontaneous movement on HA form part of the intrinsically activated phenotype of HCs. Interleukin-8 (IL-8) inhibited HC movement on HA, and this cell arrest was accompanied by increased actin polymerization and a more pronounced association of CD44 with the cytoskeleton. All of these findings are in sharp contrast to our previous observations with chronic lymphocytic leukemia cells, which are nonmotile on HA, but in response to IL-8 become polarized and motile using the receptor for HA-mediated motility rather than their apparently inactive CD44. Immunohistochemical examination of HCL tissues showed the ubiquitous presence of IL-8 and the prominence of HA in bone marrow stroma and hepatic portal tracts. This suggests that CD44-HA interactions are important in HC homing to these sites, but not to splenic red pulp or hepatic sinusoids, where HA is largely absent. Moreover, engagement of CD44 on HCs stimulates fibronectin synthesis, an observation that is likely to be relevant to the restriction of fibrosis in the disease to HC-infiltrated areas containing HA.


Blood ◽  
1982 ◽  
Vol 59 (1) ◽  
pp. 52-60 ◽  
Author(s):  
J Jansen ◽  
HR Schuit ◽  
CJ Meijer ◽  
JA van Nieuwkoop ◽  
W Hijmans

Abstract To determine the maturation arrest of the neoplastic cells of hairy- cell leukemia (HCL) and the spectrum of the surface markers on these cells, a series of 51 patients with this disease was studied. The cells of all but two of the patients showed monoclonal surface Ig with respect to light chains. In about one-third of the cases, only gamma heavy chain determinants were present on the cells; the majority carried multiple heavy chain determinants as documented by the application of different fluorochromes. Two patients each showed two different clones of cells, both of the same light chain type. In one of these two patients, two paraproteins were present in the serum. Intracytoplasmic Ig was found in only 4 of 39 cases, in all instances being IgM. All cases studied concerned cells with FclgG receptors; however, the density of this receptor varied. FcIgM receptors also showed a spectrum of density, with some cases showing very few FcIgM- positive cells. Receptors C3 were not observed on the hairy cells. Serum immunoglobulin levels were normal or increased. Paraproteins were found in the sera of 4 of 38 patients. These data suggest that HCL is a neoplasm of B lymphocytes. The neoplastic cells are probably arrested at a more mature stage than the cells of chronic lymphocytic leukemia. The multiple isotypes on the cells indicate a block at the “switch” phase from the small micro-carrying lymphocyte to the larger Ig- producing lymphocyte or plasma cell.


Blood ◽  
1989 ◽  
Vol 74 (1) ◽  
pp. 320-325 ◽  
Author(s):  
L Visser ◽  
A Shaw ◽  
J Slupsky ◽  
H Vos ◽  
S Poppema

Monoclonal antibodies reactive with hairy cell leukemia were developed to aid in the diagnosis of this subtype of B cell chronic lymphocytic leukemia and to gain better insight into the origin of hairy cells. Three antibodies were found to be of value in the diagnosis of hairy cell leukemia. Antibody B-ly 2 can be considered a pan-B cell reagent and generally reacts similar to CD22 antibodies. Antibody B-ly 6 is reactive with the same antigen as CD11c (p150/95), an antigen that is present on hairy cell leukemia, macrophages, and a minor subpopulation of lymphocytes. Antibody B-ly 7 is a unique antibody reactive with 144 Kd antigen present only on hairy cell leukemia and a very small population of normal B lymphocytes. This subpopulation may be the counterpart of hairy cells.


Blood ◽  
1994 ◽  
Vol 83 (6) ◽  
pp. 1558-1562 ◽  
Author(s):  
E Matutes ◽  
R Morilla ◽  
K Owusu-Ankomah ◽  
A Houlihan ◽  
D Catovsky

Splenic lymphoma with villous lymphocytes (SLVL) is a low-grade disorder that regularly presents with peripheral blood involvement. We describe the immunophenotype of the circulating cells from 100 SLVL patients whose disease has been characterized on clinical, morphologic, and histologic grounds. Cells from all cases expressed B-cell antigens (CD19 and CD37) and/or HLA-Dr and showed light chain restriction (kappa/lambda: 1.5/1) with moderate to strong intensity of membrane Ig staining. Cells from most cases (> 80%) were CD24+, FMC7+, and expressed strongly membrane CD22. The monoclonal antibodies CD10, CD23, and CD38 were positive in one-third of the cases; CD11c in 47%; and CD25 in 25% of cases. A minority of cases (< 20%) were positive with HC2, B-ly-7, and CD5. However, none of the 19 CD5+ cases had the phenotype characteristic of chronic lymphocytic leukemia (CD5+, CD23+, FMC7-, weak surface Ig and membrane CD22). None of the 17 CD25+ cases had the immunophenotype typical of hairy cell leukemia (CD25+, CD11c+, HC2+, B-ly-7+). HC2 and B-ly-7 were the most useful reagents to distinguish SLVL from hairy cell leukemia. Our findings demonstrate that SLVL has a distinct immunologic profile and that monoclonal antibodies are important for the differential diagnosis between this disease and other B-lymphoproliferative disorders with which SLVL can be confused.


1994 ◽  
Vol 15 (1-2) ◽  
pp. 167-172 ◽  
Author(s):  
Antonio Cuneo ◽  
Renato Bigoni ◽  
Massimo Balboni ◽  
Maria Gretel Carli ◽  
Nadia Piva ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Alexia Vereertbrugghen ◽  
Ana Colado ◽  
Ernesto Gargiulo ◽  
Raimundo Fernando Bezares ◽  
Horacio Fernández Grecco ◽  
...  

Current standard treatment of patients with hairy cell leukemia (HCL), a chronic B-cell neoplasia of low incidence that affects the elderly, is based on the administration of purine analogs such as cladribine. This chemotherapy approach shows satisfactory responses, but the disease relapses, often repeatedly. Venetoclax (ABT-199) is a Bcl-2 inhibitor currently approved for the treatment of chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) in adult patients ineligible for intensive chemotherapy. Given that HCL cells express Bcl-2, our aim was to evaluate venetoclax as a potential therapy for HCL. We found that clinically relevant concentrations of venetoclax (0.1 and 1 µM) induced primary HCL cell apoptosis in vitro as measured by flow cytometry using Annexin V staining. As microenvironment induces resistance to venetoclax in CLL, we also evaluated its effect in HCL by testing the following stimuli: activated T lymphocytes, stromal cells, TLR-9 agonist CpG, and TLR-2 agonist PAM3. We found decreased levels of venetoclax-induced cytotoxicity in HCL cells exposed for 48 h to any of these stimuli, suggesting that leukemic B cells from HCL patients are sensitive to venetoclax, but this sensitivity can be overcome by signals from the microenvironment. We propose that the combination of venetoclax with drugs that target the microenvironment might improve its efficacy in HCL.


Author(s):  
Anindita Novia Damayanti ◽  
Arifoel Hajat

Hairy Cell Leukemia (HCL) is a lymphoproliferative B cell abnormality dominated by mature lymphocytes with cytoplasmic projections and often misunderstood as Chronic Lymphocytic Leukemia (CLL). Misdiagnosis can be caused by errors in the preparation of peripheral Blood Smear Evaluation (BSE). Immunophenotyping is an option to differentiate HCL from CLL. A 56-year-old female presented with complaints of weakness. Physical examination showed conjunctival anemia 3 3 and hepatosplenomegaly. Hematological test results were as follows: Hb 7.4 g/dL; WBC 131.24x10 /uL; and Plt 61x10 /uL. BSE And Bone Marrow Aspiration (BMA) showed predominantly mature lymphocytes with cytoplasmic projections and suspected CLL with HCL as the differential diagnosis. Immunophenotyping with peripheral blood samples showed CD19+, CD20+, CD79a+, HLA-DR+, CD5-, and CD7- suggesting an increasing mature lymphocytes population (74.16%) that expressed B lymphoid lineage. White Precursor Cell (WPC) channel test showed an abnormal lymphocytes population. The differential diagnosis of patients with dominant mature lymphocytes BSE with cytoplasmic projections was CLL and HCL. Immunophenotyping of CLL showed positive results on B cell markers (CD19, CD20, CD79a, and HLA-DR) with aberrant CD5. However, in such an HCL case like this, there were strongly positive results on B cell markers but the absence of aberrant CD5. This study was supported by the presence of abnormal lymphocytes population in the WPC test. The diagnosis of HCL in this patient was based on interpretation of BSE and immunophenotyping, supported by the WPC test.


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