Phenotypic analysis of hairy cell leukemia: "variant" cases express the interleukin-2 receptor beta chain, but not the alpha chain (CD25)

Hairy cell leukemia (HCL) is a B-cell chronic lymphoproliferative disorder in which the pathologic cells show a strong expression of CD25 (interleukin-2 [IL-2] receptor alpha chain or p55). “Variant” cases of HCL, characterized by hyperleukocytosis, neoplastic elements with a prominent nucleolus and a higher nucleo/cytoplasmic ratio, and an easily obtained bone marrow aspirate, lack surface CD25 determinants. Limited information is available on the expression of the IL-2 receptor beta chain (p75) on normal and neoplastic B cells. In this study, we have assessed by immunofluorescence and mRNA analysis the presence of the IL-2 receptor alpha and beta chains on 12 cases of classic HCL, as well as on 3 variant cases. The results obtained show that, while the alpha chain of the IL-2 receptor is present only on classic HCL, the IL- 2 receptor beta chain (p75) is expressed on both the classic and variant form. Unlike hairy cells, only 8 of the 15 B-cell chronic lymphocytic leukemia cases tested showed a weak expression of the p75 antigen on a small proportion of cells. Purified B lymphocytes from normal healthy controls, as well as Epstein-Barr virus-transformed lymphoblastoid cell lines, showed a weak staining for the p75 determinant, while being CD25-. The results of this study suggest that the expression of the alpha and beta chains of the IL-2 receptor appears to be upregulated or downregulated during the process of B-cell- lineage activation and differentiation.

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Phenotypic analysis of hairy cell leukemia: "variant" cases express the interleukin-2 receptor beta chain, but not the alpha chain (CD25)

Blood ◽

10.1182/blood.v82.2.528.528 ◽

1993 ◽

Vol 82 (2) ◽

pp. 528-535 ◽

Cited By ~ 26

Author(s):

D de Totero ◽

PL Tazzari ◽

F Lauria ◽

D Raspadori ◽

PF di Celle ◽

...

Keyword(s):

B Cell ◽

Hairy Cell Leukemia ◽

Interleukin 2 ◽

Variant Form ◽

Hairy Cell ◽

Beta Chain ◽

Cell Leukemia ◽

Receptor Alpha ◽

Alpha Chain ◽

Receptor Beta

Abstract Hairy cell leukemia (HCL) is a B-cell chronic lymphoproliferative disorder in which the pathologic cells show a strong expression of CD25 (interleukin-2 [IL-2] receptor alpha chain or p55). “Variant” cases of HCL, characterized by hyperleukocytosis, neoplastic elements with a prominent nucleolus and a higher nucleo/cytoplasmic ratio, and an easily obtained bone marrow aspirate, lack surface CD25 determinants. Limited information is available on the expression of the IL-2 receptor beta chain (p75) on normal and neoplastic B cells. In this study, we have assessed by immunofluorescence and mRNA analysis the presence of the IL-2 receptor alpha and beta chains on 12 cases of classic HCL, as well as on 3 variant cases. The results obtained show that, while the alpha chain of the IL-2 receptor is present only on classic HCL, the IL- 2 receptor beta chain (p75) is expressed on both the classic and variant form. Unlike hairy cells, only 8 of the 15 B-cell chronic lymphocytic leukemia cases tested showed a weak expression of the p75 antigen on a small proportion of cells. Purified B lymphocytes from normal healthy controls, as well as Epstein-Barr virus-transformed lymphoblastoid cell lines, showed a weak staining for the p75 determinant, while being CD25-. The results of this study suggest that the expression of the alpha and beta chains of the IL-2 receptor appears to be upregulated or downregulated during the process of B-cell- lineage activation and differentiation.

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Polyclonal B-Cell Lymphocytosis With Features Resembling Hairy Cell Leukemia-Japanese Variant

Blood ◽

10.1182/blood.v89.6.2008 ◽

1997 ◽

Vol 89 (6) ◽

pp. 2008-2014 ◽

Cited By ~ 21

Author(s):

Takashi Machii ◽

Mitsuhiro Yamaguchi ◽

Ryoichi Inoue ◽

Yukihiro Tokumine ◽

Hirohiko Kuratsune ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Hairy Cell Leukemia ◽

Leukemia Cells ◽

Tartrate Resistant Acid Phosphatase ◽

Variant Form ◽

Hairy Cell ◽

Cell Leukemia ◽

Persistent Lymphocytosis ◽

Biopsy Specimens

Abstract Polyclonal B lymphocytosis was found in four patients having clinical and hematologic features resembling those of hairy cell leukemia (HCL). All four patients were women between 37 and 67 years of age. Three patients had splenomegaly. Lymphadenopthy was absent or slight. Persistent lymphocytosis was seen in all the patients, and anemia and/or thrombopenia was observed in three of the patients. Abnormal lymphocytes have long microvilli and prominent membranous ruffles on their surfaces. Bone marrow aspirates and biopsy specimens showed increased numbers of abnormal lymphocytes with round nuclei and abundant pale cytoplasm. Although these findings were similar to those of HCL, studies of Ig gene rearrangements and expression showed the polyclonal proliferation of B cells. We called this new disease hairy B-cell lymphoproliferative disorder (HBLD). All four patients exhibited a polyclonal increase in serum IgG. The morphology of the cells in HBLD was more similar to that of leukemia cells of a variant form of HCL (HCL-Japanese variant) than to typical HCL cells. The surface IgG+, CD5−, CD11c+, CD22+, CD24−, CD25− phenotype and the weak tartrate-resistant acid phosphatase activity in the cells were identical to those of HCL cells of the Japanese variant. Our findings suggest that the B cells in HBLD are the nonmalignant counterpart of leukemic B cells in HCL-Japanese variant.

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Involvement of HLA Antigens, Interleukin 2 Receptor and B-Cell Growth Factor in Interferon Action in Hairy Cell Leukemia

Leukemia & Lymphoma ◽

10.3109/10428199009053529 ◽

1990 ◽

Vol 2 (3-4) ◽

pp. 235-242 ◽

Cited By ~ 1

Author(s):

Haim Gamliel ◽

Dorit Gurfel ◽

Shi-Hua Wu ◽

Samuel Salzberg ◽

Harvey M Golomb

Keyword(s):

Growth Factor ◽

Cell Growth ◽

B Cell ◽

Hairy Cell Leukemia ◽

Interleukin 2 ◽

Hla Antigens ◽

Hairy Cell ◽

Cell Leukemia ◽

Interleukin 2 Receptor ◽

B Cell Growth Factor

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VH gene analysis of hairy cell leukemia reveals a homogeneous mutation status and suggests its marginal zone B-cell origin

Leukemia ◽

10.1038/sj.leu.2403503 ◽

2004 ◽

Vol 18 (10) ◽

pp. 1729-1732 ◽

Cited By ~ 31

Author(s):

V Vanhentenrijk ◽

A Tierens ◽

I Wlodarska ◽

G Verhoef ◽

C D Wolf-Peeters

Keyword(s):

B Cell ◽

Hairy Cell Leukemia ◽

Marginal Zone ◽

Gene Analysis ◽

Hairy Cell ◽

Cell Leukemia ◽

Mutation Status ◽

Vh Gene

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Serum Soluble Interleukin-2 Receptor Levels in Hairy Cell Leukemia: Correlation with Clinical and Hematological Parameters and with α-Interferon Treatment

Leukemia & Lymphoma ◽

10.3109/10428199209053608 ◽

1992 ◽

Vol 7 (1-2) ◽

pp. 103-107 ◽

Cited By ~ 9

Author(s):

Francesco Lauria ◽

Damiano Rondelli ◽

Donatella Raspadori ◽

Pier Luigi Zinzani ◽

Donatella Benfenati ◽

...

Keyword(s):

Hairy Cell Leukemia ◽

Hematological Parameters ◽

Interleukin 2 ◽

Interferon Treatment ◽

Hairy Cell ◽

Cell Leukemia ◽

Interleukin 2 Receptor ◽

Soluble Interleukin 2 Receptor

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BRAF mutation in hairy cell leukemia

Oncology Reviews ◽

10.4081/oncol.2014.253 ◽

2014 ◽

Cited By ~ 6

Author(s):

Ahmad Ahmadzadeh ◽

Saeid Shahrabi ◽

Kaveh Jaseb ◽

Fatemeh Norozi ◽

Mohammad Shahjahani ◽

...

Keyword(s):

B Cell ◽

Hairy Cell Leukemia ◽

Mapk Signaling ◽

Mitogen Activated Protein Kinase ◽

Braf V600e ◽

Common Mutation ◽

Hairy Cell ◽

Cell Leukemia ◽

Mitogen Activated Protein ◽

Almost All

BRAF is a serine/threonine kinase with a regulatory role in the mitogen-activated protein kinase (MAPK) signaling pathway. A mutation in the RAF gene, especially in BRAF protein, leads to an increased stimulation of this cascade, causing uncontrolled cell division and development of malignancy. Several mutations have been observed in the gene coding for this protein in a variety of human malignancies, including hairy cell leukemia (HCL). BRAF V600E is the most common mutation reported in exon15 of BRAF, which is observed in almost all cases of classic HCL, but it is negative in other B-cell malignancies, including the HCL variant. Therefore it can be used as a marker to differentiate between these B-cell disorders. We also discuss the interaction between miRNAs and signaling pathways, including MAPK, in HCL. When this mutation is present, the use of BRAF protein inhibitors may represent an effective treatment. In this review we have evaluated the role of the mutation of the BRAF gene in the pathogenesis and progression of HCL.

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Small B cell lymphomas and leukemias including hairy cell leukemia

The Lymphoid Neoplasms 3ed ◽

10.1201/b13424-78 ◽

2010 ◽

pp. 1213-1237

Keyword(s):

B Cell ◽

Hairy Cell Leukemia ◽

Hairy Cell ◽

Cell Leukemia ◽

B Cell Lymphomas

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Hairy cell leukemia: a tumor of pre-plasma cells

Blood ◽

10.1182/blood.v65.3.620.bloodjournal653620 ◽

1985 ◽

Vol 65 (3) ◽

pp. 620-629 ◽

Cited By ~ 1

Author(s):

KC Anderson ◽

AW Boyd ◽

DC Fisher ◽

D Leslie ◽

SF Schlossman ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Plasma Cell ◽

Hairy Cell Leukemia ◽

Plasma Cells ◽

Tartrate Resistant Acid Phosphatase ◽

Hairy Cell ◽

Cell Leukemia ◽

Cell Surface Antigens ◽

Hairy Cells

Monoclonal antibodies defining B-, T-, and myeloid-restricted cell surface antigens were used to characterize the lineage and state of differentiation of tumor cells isolated from 22 patients with hairy cell leukemia (HCL). These tumors were shown to be of B lineage because they strongly expressed the B cell-restricted antigens B1 and B4 and lacked T cell- and monocyte-restricted antigens. Moreover, the strong expression of the plasma cell-associated PCA-1 antigen on the majority of hairy cells suggested that these tumors correspond to later stages of B cell ontogeny. Dual fluorescence experiments further confirmed that HCL splenocytes that coexpressed B1 and PCA-1 demonstrated both the morphology and tartrate-resistant acid phosphatase positivity of hairy cells. The observation that some hairy cells either spontaneously produce immunoglobulin (Ig) or could be induced to proliferate and secrete Ig provides complementary support for the view that HCL is a pre-plasma cell tumor. However, staining of hairy cells with anti-IL2R1 monoclonal antibody, which is directed to the T cell growth factor receptor and/or with the anti-Mo1 reagent, directed to C3bi complement receptor, distinguish these cells from currently identified B cells.

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Monoclonal antibodies reactive with hairy cell leukemia [see comments]

Blood ◽

10.1182/blood.v74.1.320.bloodjournal741320 ◽

1989 ◽

Vol 74 (1) ◽

pp. 320-325 ◽

Cited By ~ 1

Author(s):

L Visser ◽

A Shaw ◽

J Slupsky ◽

H Vos ◽

S Poppema

Keyword(s):

Monoclonal Antibodies ◽

B Cell ◽

Hairy Cell Leukemia ◽

Small Population ◽

Lymphocytic Leukemia ◽

Hairy Cell ◽

Cell Leukemia ◽

Hairy Cells ◽

A Minor ◽

Insight Into

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.

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