Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anaplastic large cell lymphoma (ALCL) is a distinct clinicopathologic variant of intermediate grade non-Hodgkin's lymphomas (NHL) composed of large pleomorphic cells that usually express the CD30 antigen and interleukin (IL)-2 receptors, and is characterized by frequent cutaneous and extranodal involvement. With variable frequency ALCL bear the t(2;5)(p23;q35) chromosomal translocation that fuses the nucleophosmin (NPM) gene on chromosome 5q35 to a novel protein kinase gene, Anaplastic Lymphoma Kinase (ALK), on chromosome 2p23. We determined the frequency of this translocation with a novel DNA polymerase chain reaction (PCR) technique using 0.5 microgram of genomic DNA, 5'-primers derived from the NPM gene and 3'-primers derived from the ALK gene and hybridization with internal probes. The presence of amplifiable DNA in the samples was tested with the inclusion in the PCR reaction of oligonucleotide primers designed to amplify a 3016-bp fragment from the beta-globin locus. NMP-ALK fusion amplicons were detected using DNA isolated either from all three ALCL cell lines tested, or from all four primary ALCL tumors known to contain the t(2;5)(p23;q35) translocation. Nested amplicons were detected by hybridization in 100% of specimens diluted 10(4)-fold and in 20% of those diluted 10(5)-fold. We subsequently examined archival genomic DNA from 20 patients with ALCL, 39 with diffuse large cell, 2 with mantle cell, 20 with peripheral T cell, 13 with low-grade NHL, 31 with Hodgkin's disease (HD), and 6 with lymphomatoid papulosis. Fusion of the NPM and ALK genes was detected in three of 18 patients with ALCL who had amplifiable DNA (17%, 95% confidence intervals 4% to 41%), but not in any patients with other NHL, HD, or lymphomatoid papulosis. The amplicon sizes were different in all cell lines and patients reflecting unique genomic DNA breakpoints. We conclude that with genomic DNA-PCR the rearrangement of the NPM and ALK loci is restricted to patients with ALCL. Further studies are needed to determine the prognostic significance of the NPM-ALK rearrangement, to determine whether its detection can aid in the differential diagnosis between ALCL. Hodgkin's disease, and lymphomatoid papulosis, and to establish the usefulness of the genomic DNA PCR in the monitoring of minimal residual disease in those patients whose tumors bear the t(2;5).
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PMID:Amplification of genomic DNA demonstrates the presence of the t(2;5) (p23;q35) in anaplastic large cell lymphoma, but not in other non-Hodgkin's lymphomas, Hodgkin's disease, or lymphomatoid papulosis. 926 95

Anaplastic large cell lymphoma (ALCL) is an intermediate grade Non-Hodgkin's lymphoma (NHL) characterized by the frequent presence of the t(2;5)(p23;q35). This translocation fuses the nucleophosmin (NPM) gene on chromosome 5q35 to a protein kinase gene (Anaplastic Lymphoma Kinase, ALK) on chromosome 2p23. In order to determine the frequency of t(2;5) we used a DNA polymerase chain reaction (PCR) amplification using genomic DNA, 5'-primers derived from the NPM gene, and 3'-primers derived from the ALK gene. The presence of amplifiable DNA in the samples was established with PCR and oligonucleotide primers designed to amplify a 3,016 bp fragment from the beta-globin locus. The t(2;5) PCR assay was established using DNA isolated from three t(2;5)-positive ALCL cell lines. Its ability to amplify genomic DNA prepared for routine molecular diagnostic use was validated using archival DNA from four ALCL tumors known to be t(2;5)-positive. Its sensitivity was established by serially diluting t(2;5)-positive DNA in normal DNA: amplicons were generated in 100% of reactions diluted 10(4)-fold (6-8 cells per tube) and in 30% of those diluted 10(5)-fold (0.6-0.8 cells per tube.) We subsequently analyzed archival genomic DNA extracted from 38 ALCL, 77 NHLs, 37 Hodgkin's lymphomas, and 9 lymphomatoid papuloses. The t(2;5) was detected in 6 ALCLs (16%, 95% confidence intervals 6%-31%), but not in any other lymphoma, or in lymphomatoid papulosis. By using the published sequence of the fourth NPM intron that is involved in t(2;5) and by sequencing the individual tumor amplicons and also the normal ALK intron that is involved in t(2;5), we established that all breakpoints involve the same introns in the ALK and NPM loci. Detailed analysis demonstrated that each translocation generates a unique breakpoint sequence, and suggested that sequence homology between the ALK and NPM intron sequences may be involved in the translocation. We conclude that genomic DNA-PCR is useful for the detection of t(2;5) that in our patient population is restricted to ALCL and is not detectable in other NHL, Hodgkin's disease, or lymphomatoid papulosis. More work is needed to determine the prognostic significance of t(2;5), and to establish the utility of the genomic DNA PCR in monitoring minimal residual disease.
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PMID:Genomic DNA amplification and the detection of t(2;5)(p23;q35) in lymphoid neoplasms. 964 64

Lymphomatous involvement of the airway causing stridor is a rare but frightening presentation of an eminently treatable condition. We describe a 24-year-old woman with tracheal non-Hodgkin lymphoma who was initially diagnosed with asthma, but subsequently presented with near-fatal acute upper airway obstruction because of a tracheal Anaplastic Lymphoma Kinase (ALK)+ anaplastic T-cell lymphoma. The obstructing tumor was extricated by means of rigid bronchoscopy. After six cycles of Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone chemotherapy, the patient went into complete clinical remission. A high index of suspicion in patients with dyspnoea and wheeze unresponsive to bronchodilators is crucial in early diagnosis of tracheal tumors.
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PMID:Primary tracheal lymphoma causing respiratory failure. 1867 Mar 14

The discovery of microRNA (miRNA) has provided new and powerful tools for studying the mechanism, diagnosis and treatment of human cancers. The down-regulation of tumor suppressive miRNA by hypermethylation of CpG island (CpG is shorthand for 5'-C-phosphate-G-3', that is, cytosine and guanine separated by only one phosphate) is emerging as a common hallmark of cancer and appears to be involved in drug resistance. This review discusses the role of miRNA and DNA methylation in drug resistance mechanisms and highlights their potential as anti-cancer therapies in Anaplastic Lymphoma Kinase (ALK)-positive lymphomas. These are a sub-type of non-Hodgkin's lymphomas that predominantly affect children and young adults and are characterized by the expression of the nucleophosmin (NPM)/ALK chimeric oncoprotein. Dysregulation of miRNA expression and regulation has been shown to affect several signaling pathways in ALK carcinogenesis and control tumor growth, both in cell lines and mouse models. These data suggest that the modulation of DNA methylation and/or the expression of these miRNA could serve as new biomarkers and have potential therapeutic applications for ALK-positive malignancies.
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PMID:Crosstalk between microRNA and DNA Methylation Offers Potential Biomarkers and Targeted Therapies in ALK-Positive Lymphomas. 2877 Nov 64

Anaplastic Large Cell Lymphomas (ALCL) are clinically aggressive and pathologically distinct lymphoid neoplasms that originate from a mature post-thymic T-cell. The contemporary World Health Organization (WHO) Classification of Haematologic Malignancies recognizes two distinct subtypes of systemic ALCL: Anaplastic Lymphoma Kinase (ALK)-negative, and ALK-positive. An additional unique subtype of ALCL is known to arise after prolonged exposure to breast implants, known as Breast Implant Associated ALCL (BIALCL). While histologic features of ALCL subtypes have significant overlap, genomic studies suggest the unique pathophysiology and molecular events of tumorigenesis. As a group, ALCLs are rare among non-Hodgkin lymphomas comprising 1-3% overall. There seems to be age and geographic predilection with ALK-positive ALCL affecting younger individuals and being diagnosed more frequently in North America than Europe. Both subtypes are quite uncommon in Hispanic and Asian populations. ALK-positive ALCL patients have a better overall prognosis than those with ALK-negative ALCL, and clinical features at presentation (i.e., International Prognostic Index, IPI) define the outcome in both subtypes. Molecular events affecting DUSP22 and TP63 have been reported to predict survival outcomes as well, with former being favorable, and the latter an unfavorable prognostic marker. Multiagent CHOP-like chemotherapy remains a standard of care for newly diagnosed ALCL patients treated with curative intent and provide a chance of cure for the majority of ALK-positive ALCL patients, and at least half of the ALK-negative ALCL patients. The role of consolidative high-dose therapy and autologous hematopoietic stem cell transplantation remains unclear. Novel targeted agents are actively being investigated for their role in initial therapy. New immunoconjugates, targeted kinase inhibitors, and transgenic autologous T-cells are being studied in patients with relapsed and refractory disease. This review will discuss contemporary concepts in pathogenesis and management of systemic ALCL. The biology and management of primary cutaneous ALCL will be discussed elsewhere.
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PMID:Anaplastic Large Cell Lymphoma: Contemporary Concepts and Optimal Management. 3059 16

Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK+LBCL) is a rare non-Hodgkin lymphoma that exhibits a characteristic immunoblastic/plasmablastic morphology and is frequently expressing Clathrin-anaplastic lymphoma kinase fusion protein. Since being negative for T- and B- linage markers, this tumor is easy to be misdiagnosed, especially when it has unusual morphology and immunophenotype. Here, we report an ALK+LBCL with a diagnostic pitfall of carcinoma. The patient was a 28-year-old man with enlargement of a right submandibular lymph node. Morphologically, the lymph node had an unusual nodular growth pattern, with nodules surrounded by collagen bands. The neoplastic cells expressed epithelial membrane antigen, CD138, CD38, Mum-1, but negative for T- and B- linage markers, and showed a strong granular cytoplasmic Anaplastic Lymphoma Kinase staining pattern. Some tumor cells had the expressing of Cytokeratin.
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PMID:Anaplastic lymphoma kinase-positive large B-cell lymphoma with a diagnostic pitfall of carcinoma: a case report. 3196 73

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare, non-Hodgkin lymphoma which arises within the capsules of breast implants. These particular tumours have expression of CD30 and are negative for Anaplastic Lymphoma Kinase (ALK). Here, we report a case of BIA-ALCL in a 48-year-old woman post breast reconstruction. This case report is aimed at raising awareness and education on the significance of considering the development of BIA-ALCL in cases where cytology is negative and helping better understand this disease process.
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PMID:Breast Implant-Associated Anaplastic Large Cell Lymphoma. 3255 34