scholarly journals Clinical Significance of Alk-1 Gene Abnormalities in Diffuse Large Cell Lymphoma

2012 ◽  
Vol 6 ◽  
pp. CMO.S9920
Author(s):  
L. Korashy ◽  
H. El-Zawahry ◽  
S. Abdou ◽  
D. Shahin ◽  
F. Sherif ◽  
...  

Objectives To detect relative frequency of anaplastic lymphoma kinase (ALK-1) gene abnormality in diffuse large cell lymphoma (DLCL) using fluorescence in situ hybridization (FISH), and correlate its presence with clinicopathological features which may be useful for choice of therapy and predict survival in newly diagnosed cases. Patients and Methods A prospective study was done between March 2004 and October 2009. Fifty patients newly diagnosed with DLCL were enrolled into the study. Immunophenotyping was done and detection of ALK-1 gene abnormalities were carried out by immunohistochemically (IHC) and FISH. Patients that proved to be ALK-1 positive were treated with standard cyclophosphamide –hydroxydaunorubicin-oncovin-prednisone (CHOP) protocol. Results All ALK +ve patients achieved complete remission (CR) vs. 93.5% CR and 6.5% partial remission (PR) for ALK –ve patients respectively. Disease free survival (DFS) at 24 months was 81.8% in the CHOP-14 group (ALK-1−) vs. 100% for the CHOP-21 group (ALK-1+). Overall survival (OS) at 30 months was 80.4% in the CHOP-14 group vs. 100% for the CHOP-21 group.

2002 ◽  
Vol 132 (2) ◽  
pp. 125-132 ◽  
Author(s):  
Bhavana J. Dave ◽  
Marilu Nelson ◽  
Diane L. Pickering ◽  
Wing C. Chan ◽  
Timothy C. Greiner ◽  
...  

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 253
Author(s):  
Federica Lovisa ◽  
Anna Garbin ◽  
Sara Crotti ◽  
Piero Di Battista ◽  
Ilaria Gallingani ◽  
...  

Over the past 15 years, several biological and pathological characteristics proved their significance in pediatric anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma (ALCL) prognostic stratification. However, the identification of new non-invasive disease biomarkers, relying on the most important disease mechanisms, is still necessary. In recent years, plasmatic circulating small extracellular vesicles (S-EVs) gathered great importance both as stable biomarker carriers and active players in tumorigenesis. In the present work, we performed a comprehensive study on the proteomic composition of plasmatic S-EVs of pediatric ALCL patients compared to healthy donors (HDs). By using a mass spectrometry-based proteomics approach, we identified 50 proteins significantly overrepresented in S-EVs of ALCL patients. Gene Ontology enrichment analysis disclosed cellular components and molecular functions connected with S-EV origin and vesicular trafficking, whereas cell adhesion, glycosaminoglycan metabolic process, extracellular matrix organization, collagen fibril organization and acute phase response were the most enriched biological processes. Of importance, consistently with the presence of nucleophosmin (NPM)-ALK fusion protein in ALCL cells, a topological enrichment analysis based on Reactome- and Kyoto Encyclopedia of Genes and Genomes (KEGG)-derived networks highlighted a dramatic increase in proteins of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway in ALCL S-EVs, which included heat shock protein 90-kDa isoform alpha 1 (HSP90AA1), osteopontin (SPP1/OPN) and tenascin C (TNC). These results were validated by Western blotting analysis on a panel of ALCL and HD cases. Further research is warranted to better define the role of these S-EV proteins as diagnostic and, possibly, prognostic parameters at diagnosis and for ALCL disease monitoring.


Blood ◽  
1987 ◽  
Vol 70 (1) ◽  
pp. 45-50 ◽  
Author(s):  
LF Bertoli ◽  
H Kubagawa ◽  
GV Borzillo ◽  
M Mayumi ◽  
JT Prchal ◽  
...  

Abstract A murine monoclonal antibody made against an idiotypic determinant (Id) of surface IgM/IgD lambda molecules on chronic lymphocytic leukemia (CLL) cells of a 71-year-old woman was used for clonal analysis by two- color immunofluorescence. The anti-Id antibody identified IgM+/IgD+/lambda+ B cells as the predominant cell type of her CLL clone. In addition, substantial proportions of the IgG and IgA B cells and most of the IgM plasma cells in her bone marrow and blood were Id+. Six years after diagnosis, the patient died of respiratory failure due to infiltration of lungs by malignant cells. Autopsy revealed a dramatic change in the tumor cell morphology. The lungs, hilar nodes, and liver were infiltrated by a diffuse large cell lymphoma admixed with the leukemic cells. By immunohistologic staining these anaplastic lymphoma cells were IgM+/IgD-/lambda+ B cells expressing the same Id noted earlier on the CLL cells. The immunoglobulin gene rearrangement pattern on Southern blot analysis was also the same in leukemic blood cells and in the tissues involved by the lymphoma. Thus, the combination of antiidiotype and immunoglobulin gene analyses in this patient with Richter's syndrome revealed that a CLL clone, seemingly “frozen” in differentiation, was actually undergoing isotype switching, differentiation into plasma cells, and evolution into a rapidly growing and fetal lymphoma.


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