PRAD1, a candidate BCL1 oncogene: mapping and expression in centrocytic lymphoma.

Rosenberg, Carol L.; Wong, Emily; Petty, Elizabeth M.; Bale, Allen E.; Tsujimoto, Yoshihide; Harris, N L; Arnold, Andrew

doi:10.1073/pnas.88.21.9638

Cited by 387 publications

(169 citation statements)

References 40 publications

(38 reference statements)

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“…The distinction of MCL from other entities is clinically important because of its poor response to therapy and its unfavorable prognosis (8). Since of the description of cyclin D1 overexpression as a consistent feature of MCL and the availability of antibodies suitable for paraffin-embedded tissue, immunostaining for cyclin D1 has become an important adjunct for the diagnosis of MCL (8,13,15,33). Nevertheless, immunohistochemical demonstration of cyclin D1 can be capricious, especially in routinely processed and decalcified BM biopsy specimens, and a negative result does not rule out a diagnosis of MCL (6,16).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the distinction of MCL from other B-cell neoplasms in BM biopsies is of significant clinical relevance. Immunohistochemical demonstration of cyclin D1 protein is an important marker for the diagnosis of MCL, because it is expressed neither in normal lymphocytes nor in most B-cell NHL (6,8,13,14). However, cyclin D1 staining can be capricious in decalcified BM biopsies, and false negative results may lead to misclassification of lymphoma infiltrates (6,15,16).…”

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confidence: 99%

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p27Kip1 Immunostaining for the Differential Diagnosis of Small B-Cell Neoplasms in Trephine Bone Marrow Biopsies

et al. 2001

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The distinction between mantle cell lymphoma (MCL) and other small B-cell non-Hodgkin lymphomas (NHL) is important because MCL has a more aggressive clinical course. In bone marrow (BM) biopsy specimens, this distinction can be particularly difficult. Although cyclin D1 immunostaining and molecular detection of the t(11;14) translocation are highly specific markers for MCL, they fail to detect a proportion of cases. We have recently described that MCL typically lacks detectable expression of the cyclin-dependent kinase inhibitor p27 kip1 protein by immunostaining, which is expressed at high levels in most small B-cell NHL inversely correlated to the proliferation rate. We therefore examined whether p27 kip1 immunostaining could be a useful adjunct for the differential diagnosis of small B-cell NHL infiltrates in the BM. Trephine BM biopsy specimens of 96 patients, including well-characterized MCL (19 cases), B-cell chronic lymphocytic leukemia (27 cases), follicular lymphoma (18 cases), hairy cell leukemia (22 cases), and marginal zone lymphoma (10 cases) as well as 10 reactive BM, including five with benign lymphoid aggregates were investigated. In addition, the presence of a t(11;14) translocation involving the major translocation cluster was studied by PCR in all MCL. All cases of B-cell chronic lymphocytic leukemia, follicular lymphoma, and marginal zone lymphoma revealed a strong p27 kip1 nuclear staining in the majority of neoplastic cells. Fourteen (78%) cases of MCL were p27 kip1 -negative in the tumor cells, whereas four cases revealed a weak nuclear positivity. Seventeen (77%) cases of hairy cell leukemia were also either completely negative for p27 kip1 or showed a faint positive staining in a minority of the neoplastic cells. Nine of 19 cases (47%) of MCL showed a bcl1 rearrangement involving the major translocation cluster region. These findings demonstrate that p27 kip1 immunostaining is a valuable additional marker for the differential diagnosis of small B-cell NHL infiltrates in BM biopsies. The reduction or lack of p27 kip1 protein expression in MCL, as well as in hairy cell leukemia, might be an important event in the pathogenesis of these disorders.KEY WORDS: p27 kip1 protein, Bone marrow infiltrates, Differential diagnosis, Hairy cell leukemia, Immunohistochemistry, Mantle cell lymphoma, Small B-cell non-Hodgkin lymphoma.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

p27Kip1 Immunostaining for the Differential Diagnosis of Small B-Cell Neoplasms in Trephine Bone Marrow Biopsies

et al. 2001

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“…16,18,20 Especially for lymphoid neoplasias several alterations of G 1 /S phase-regulating genes have been reported. Overexpression of cyclin D1 which acts as a positive regulator of G 1 phase progression by rearrangement of the bcl-1/PRAD1 locus on chromosome 11q13 with the immunoglobulin heavy chain gene on chromosome 14q23, 19 is the hallmark of mantle cell lymphoma 21 and has also been described in multiple myeloma 22 and atypical chronic lymphocytic leukemia. 23 In addition, homozygous deletions of the p16 INK4A and p16 INK4B CDK-inhibitor genes and loss of Rb expression are among the most frequently observed abnormalities in lymphoid tumors.…”

Section: Introductionmentioning

confidence: 99%

Cyclin A1 is predominantly expressed in hematological malignancies with myeloid differentiation

et al. 1998

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Cyclin A is a cell cycle regulatory protein that functions in mitotic and S phase control in mammalian cells. However, in contrast to other G 1 phase regulatory proteins, such as cyclin D, retinoblastoma protein and p16 INK4A , cyclin A seems not to be commonly involved in tumorigenesis. Recently, a second human cyclin A -cyclin A1 -has been identified. In contrast to cyclin A which is expressed throughout embryonic development and in adult tissue, the expression of cyclin A1 has been reported to be restricted to embryonic and germ line cells. We have confirmed the absence of cyclin A1 mRNA from normal peripheral blood leukocytes of seven healthy donors by single step reverse transcriptase-polymerase chain reaction (RT-PCR). Furthermore, we have examined the expression of cyclin A1 mRNA in 173 peripheral blood samples of 162 patients with various hematological malignancies. Cyclin A1 mRNA was detectable in 11 of 11 patients with acute myeloid leukemia, three of three patients with acute biphenotypic leukemia, eight of eight patients with myelodysplastic syndrome, 59 of 69 patients with chronic myelogenous leukemia (CML) at diagnosis, 13 of 15 patients with CML in blastic transformation, 10 of 18 patients with chronic lymphocytic leukemia, two of nine patients with essential thrombocythemia, and only two of 10 patients with acute lymphoblastic leukemia (ALL) with both cyclin A1 RT-PCR positive ALL leukemias being undifferentiated relapses. In addition, cyclin A1 mRNA was found in one of six leukapheresis products, harvested from individuals without hematological disorders. Taken together, cyclin A1 is expressed in the majority of myeloid and undifferentiated hematological malignancies as well as in normal hematopoietic progenitor cells. We conclude that cyclin A1, a protein potentially involved in G 1 /S phase progression of immature cells, might be necessary for proliferation of early hematopoietic progenitor cells and their leukemic counterparts being blocked at that stage of differentiation.

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“…The oncogene cyclin D1 is telomeric to the breakpoint regions and, as a result of the translocation, becomes overexpressed in lymphocytes when normally it is absent or present only at very low levels (8). Cyclin D1 protein binds to a cell cycle kinase p34 cdc2 and drives cells from G 1 into the S phase.…”

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Immunohistochemical Detection of Cyclin D1 Using Optimized Conditions Is Highly Specific for Mantle Cell Lymphoma and Hairy Cell Leukemia

et al. 2000

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Mantle cell lymphoma (MCL) is more aggressive when compared with other lymphomas composed of small, mature B lymphocytes. Cyclin D1 is overexpressed in MCL as a result of the translocation t(11;14)(q13;q32). Cyclin D1 immunohistochemistry in fixed, paraffin-embedded tissue contributes to the precise and reproducible diagnosis of MCL without the requirement of fresh tissue. However, its use in bone marrow biopsies is not well established. In addition, increased levels of cyclin D1 mRNA have been found in hairy cell leukemia but have not consistently been detected by immunohistochemistry. We used a polyclonal antibody and heatinduced antigen retrieval conditions to evaluate 73 fixed, paraffin-embedded bone marrow, spleen, and lymph node specimens with small B-cell infiltrates, obtained from 55 patients. Cyclin D1 was overexpressed in 13/13 specimens of MCL (usually strong, diffuse reactivity in most tumor cells) and in 14/14 specimens of hairy cell leukemia (usually weak, in a subpopulation of tumor cells). No reactivity was detected in five cases of B-chronic lymphocytic leukemia; five cases of splenic marginal zone lymphoma; six cases of nodal marginal zone cell lymphoma; two cases of gastric marginal zone cell lymphoma; or ten benign lymphoid infiltrates in bone marrow, spleen, or lymph nodes. In summary, although the total number of studied cases is small and a larger series of cases may be required to confirm our data, we present optimized immunohistochemical conditions for cyclin D1 in fixed, paraffin-embedded tissue that can be useful in distinguishing MCL and hairy cell leukemia from other small B-cell neoplasms and reactive lymphoid infiltrates.

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PRAD1, a candidate BCL1 oncogene: mapping and expression in centrocytic lymphoma.

Abstract: Rearrangement oftheBCLI (B-cell lymphoma 1) region on chromosome 11q13 appears to be highly characteristic of centrocytic lymphoma and also is found fuently in other B-cell neoplasm.

Cited by 387 publications

References 40 publications

p27Kip1 Immunostaining for the Differential Diagnosis of Small B-Cell Neoplasms in Trephine Bone Marrow Biopsies

p27Kip1 Immunostaining for the Differential Diagnosis of Small B-Cell Neoplasms in Trephine Bone Marrow Biopsies

Cyclin A1 is predominantly expressed in hematological malignancies with myeloid differentiation

Immunohistochemical Detection of Cyclin D1 Using Optimized Conditions Is Highly Specific for Mantle Cell Lymphoma and Hairy Cell Leukemia

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