Open AccessJournal Article
Nucleophosmin (NPM) Gene Rearrangements in Ki-1-positive Lymphomas
TLDR
The presence of NPM gene rearrangements in HD indicates the involvement of this gene in a fraction of HD, and may identify a certain subtype in ALCL and HD which may be closely related.Abstract:
The (2;5)(p23;q35) translocation which results in the fusion of the NPM (nucleophosmin) gene on chromosome 5q35 with the novel ALK (anaplastic lymphoma kinase) gene on chromosome 2p23 [S.W. Morris et al., Science (Washington DC), 263: 1281–1284, 1994] is associated with Ki-1 (CD30)-positive anaplastic large cell lymphomas (ALCL); a group of morphologically and immunophenotypically heterogeneous high grade large cell lymphomas (LCL), which share many characteristics with Hodgkin9s disease (HD), including the presence of variable numbers of Reed-Sternberg-like cells and the expression of CD30 antigen. Using a DNA probe immediately 5′ to the NPM coding sequences, we have examined NPM gene rearrangements by Southern blotting in 5 Ki-1-positive lymphoma cell lines carrying a translocation involving the 5q35 breakpoint and in 25 Ki-positive lymphoma tumors, including 9 HD. Using this method, we detected rearrangements in all cell lines with apparent clustering of the breakpoints. Analysis of 25 Ki-1-positive lymphomas indicated that only 4 neoplasms, including two HD, had NPM gene rearrangements. Thus, our findings suggest that only a subset of ALCL has detectable involvement of the NPM gene. In addition, the presence of NPM gene rearrangements in HD indicates the involvement of this gene in a fraction of HD. Thus, NPM gene rearrangements may identify a certain subtype in ALCL and HD which may be closely related.read more
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Deconstructing a Disease: RAR, Its Fusion Partners, and Their Roles in the Pathogenesis of Acute Promyelocytic Leukemia
Ari Melnick,Jonathan D. Licht +1 more
TL;DR: The elucidation of the molecular basis of acute promyelocytic leukemia emerged as a paradigm for the connection between the bench and bedside and it became apparent that APL was, among the forms of acute myeloid leukemia, uniquely sensitive to all
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CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features.
Harald Stein,Hans-Dieter Foss,Horst Dürkop,Theresa Marafioti,Georges Delsol,Karen Pulford,Stefano Pileri,Brunangelo Falini +7 more
TL;DR: Recent immunohistologic studies suggest that ALCLs Hodgkin-like represent either cases of tumor cell-rich classic Hodgkin disease or (less commonly) ALK(+) ALCL orALK(-) ALCL, both of which have an unfavorable prognosis.
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Anaplastic large cell lymphomas expressing the novel chimeric protein p80NPM/ALK: a distinct clinicopathologic entity.
TL;DR: In this article, the authors found a novel hyperphosphorylated 80-kDa protein tyrosine kinase, p80, in ALCLs with t(2;5).
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Retrovirus-Mediated Gene Transfer of NPM-ALK Causes Lymphoid Malignancy in Mice
Martin U. Kuefer,A. Thomas Look,Karen Pulford,Frederick G. Behm,Paul K. Pattengale,David Y. Mason,Stephan W. Morris +6 more
TL;DR: In this retroviral gene transfer model, NPM-ALK expression in mice causes B-lineage large-cell lymphoma, suggesting a direct causative role for this activated fusion tyrosine kinase in human lymphoma.
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Anaplastic lymphoma kinase proteins in growth control and cancer.
TL;DR: Reports of ALK expression in a range of carcinoma‐derived cell lines together with its apparent role as a receptor for PTN and MK, both of which have been implicated in tumourigenesis, raise the possibility that ALK‐mediated signalling could play a role in the development and or progression of a number of common solid tumours.
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Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes).
Jacqueline Cordell,Brunangelo Falini,Wendy N. Erber,A. K. Ghosh,Zainalabideen Abdulaziz,S M MacDonald,Karen Pulford,Harald Stein,D Y Mason +8 more
TL;DR: The APAAP technique was found particularly suitable for labeling cell smears and for detecting low numbers of antigen-bearing cells in a specimen and could be used in conjunction with immunoperoxidase methods for double immunoenzymatic staining.
Journal ArticleDOI
Fusion of a Kinase Gene, ALK, to a Nucleolar Protein Gene, NPM, in Non-Hodgkin's Lymphoma
Stephan W. Morris,Mark N. Kirstein,Marcus B. Valentine,KG Dittmer,KG Dittmer,David N. Shapiro,David N. Shapiro,D. L. Saltman,AT Look,AT Look +9 more
TL;DR: In the predicted hybrid protein, the amino terminus of nucleophosmin (NPM) is linked to the catalytic domain of anaplastic lymphoma kinase (ALK), and unscheduled expression of the truncated ALK may contribute to malignant transformation in these lymphomas.
Journal ArticleDOI
The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells.
Harald Stein,D Y Mason,Johannes Gerdes,N O'Connor,J. S. Wainscoat,Gorm Pallesen,K C Gatter,B Falini,Georges Delsol,Hilmar Lemke,R Schwarting,Karl Lennert +11 more
TL;DR: Results obtained indicate that Ki-1 antigen is an inducible lymphoid-associated molecule that identifies a group of hitherto poorly characterized normal and neoplastic large lymphoid cells in Hodgkin's disease and Disorders in which only a minority of cells express Ki- 1 antigen probably represent lesions in whichonly some of the abnormal cells have transformed into an "activation state.
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