Variant B Cell Receptor Isotype Functions Differ in Hairy Cell Leukemia with Mutated BRAF and IGHV Genes

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.

Download Full-text

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

Download Full-text

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.

Download Full-text

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.

Download Full-text

Rearrangement of both immunoglobulin and T-cell receptor genes in a prolymphocytic variant of hairy cell leukemia patient resistant to interferon-alpha [published erratum appears in Blood 1989 Feb;73(2):624]

Blood ◽

10.1182/blood.v72.5.1708.bloodjournal7251708 ◽

1988 ◽

Vol 72 (5) ◽

pp. 1708-1716

Author(s):

SL Giardina ◽

HA Young ◽

CR Faltynek ◽

ES Jaffe ◽

JW Clark ◽

...

Keyword(s):

T Cell ◽

T Cell Receptor ◽

Peripheral Blood ◽

Hairy Cell Leukemia ◽

Cell Receptor ◽

Hairy Cell ◽

Cell Leukemia ◽

Ifn Gamma ◽

Ifn Alpha ◽

Alpha Receptors

We describe a patient with the so-called “prolymphocytic variant” form of hairy cell leukemia (HCL) resistant to treatment with interferon- alpha (IFN-alpha). Analysis of immunoglobulin (Ig) and T-cell receptor- beta (TCR beta) gene rearrangements from serial peripheral blood mononuclear cell specimens (MNCs) confirmed not only the B-cell nature of the disease, but also the subsequent emergence of a morphologically indistinguishable population of cells with a clonal TCR beta rearrangement in addition to the original Ig gene rearrangement. With the exception of a transient increase in peripheral blood T cells during treatment with deoxycoformycin (DCF), the MNCs remained essentially constant throughout therapy with no evidence of a co- existing T-cell clone to account for the TCR beta rearrangement. Although MNCs from this patient bound significantly less IFN-alpha than did MNCs from other HCL patients, the binding was of high affinity with a kd similar to that of control cells. The number of IFN-gamma receptors on our patient's MNCs was four times higher than the number of IFN-alpha receptors and was similar to the number of IFN-alpha receptors on MNCs from HCL patients responsive to IFN-alpha. While various treatments including IFN-alpha, DCF, chlorambucil, splenectomy, leukopheresis, and IFN-gamma were not able to change the clinical progression of the disease, they may have provided an opportunity for the divergent TCR beta rearranged clone to expand and displace the initially dominant clone.

Download Full-text

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.

Download Full-text