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 lymphoma kinase (ALK) positive diffuse large B-cell lymphoma (DLBCL) is a rare subtype of non-Hodgkins lymphoma. Five such cases have been described in children. We present a 9-year-old boy, in whom diagnosis of DLBCL has been established in addition to congenital multiple enchondromatosis. Immunohistopathological evaluation of tumor biopsy established the final diagnosis of ALK + DLBCL. The clathrin gene (CLTC)-ALK fusion underlying aberrant expression of ALK in the present case was demonstrated by interphase fluorescence in situ hybridization (FISH) using break-apart rearrangement probes for ALK and CLTC. The disease in this patient was highly resistant to applied chemotherapy regimens and to radiotherapy. Analysis of the disease course in our patient and review of other cases reported previously show that ALK + DLBCL can be an aggressive malignancy that can be cured with conventional chemotherapy protocols only at stage of localized disease.
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PMID:ALK-positive diffuse large B-cell lymphoma. 1585 31

In this article, we describe the morphologic and immunophenotypic features of 75 cases of pediatric anaplastic large cell lymphoma (ALCL). According to the World Health Organization classification, 49 cases were common subtype ALCL, and respectively, 3, 6, and 17 cases were small cell, lymphohistiocytic, or mixed histologic variants. Anaplastic lymphoma kinase positivity was detected in 90.7% of the tumors and, using a panel of 9 T-cell surface markers, 88% could be assigned to the T-cell lineage. A molecular analysis for the T-cell receptor gamma (TCR- gamma) and the heavy chain of the immunoglobulin H rearrangements was performed on 6/9 ALCLs with a null immunophenotype, and a TCR clonal pattern was detected in 5/6 cases. In addition, 94.1% were immunoreactive for 1 or more cytotoxic proteins (Tia1, granzyme B, or perforin), and 15% expressed CD56. Clusterin, CD83, and Pax5, respectively, expressed in 91.3%, 1.7%, and 0% of the ALCLs, were useful biomarkers for the differential diagnosis with Hodgkin's lymphomas.
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PMID:Anaplastic large cell lymphomas: a study of 75 pediatric patients. 1753 94

Anaplastic large cell lymphoma (ALCL) is a type of non-Hodgkin lymphoma composed of CD30-positive cells. Anaplastic lymphoma kinase (ALK) -1 positive ALCL frequently involves both lymph nodes and extranodal sites. While primary extranodal involvement of ALK-1 negative ALCL is rare, this case is unique in that it is a case of primary ALK-1 negative ALCL of the brain. A 79-year-old man presented with dementia-like symptoms. Neuroimaging revealed a well-enhanced mass in the left parieto-occipital region. The tumor was excised and histological diagnosis of primary ALK-1-negative ALCL was made. Primary ALK-1-negative ALCL in this case showed aggressive clinical behavior and fatal outcome. It is of great importance to avoid any delay in reaching an accurate diagnosis, as even primary ALCL of the brain is too seldom suspected clinically.
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PMID:Primary ALK-1-negative anaplastic large cell lymphoma of the brain: case report and review of the literature. 1856

Anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma (ALK+ ALCL) is an aggressive non-Hodgkin lymphoma of T/null immunophenotype that is most prevalent in children and young adults. The normal cellular counterpart of this malignancy is presumed to be the cytotoxic T lymphocyte (CTL), and this presumption is partly based on the observation that these tumour cells often express cytotoxic granules containing Granzyme B (GzB) and Perforin. Chromosomal translocations involving the gene encoding for the ALK tyrosine kinase are also characteristic of ALK+ ALCL, and the resulting fusion proteins (e.g. NPM-ALK) initiate signalling events important in ALK+ ALCL pathogenesis. These events include the elevated expression of JunB; an AP-1 family transcription factor that promotes ALK+ ALCL proliferation. In this report we demonstrate that JunB is a direct transcriptional activator of GzB and that GzB transcription is also promoted by NPM-ALK. We found that Perforin expression was not regulated by JunB, but was promoted by NPM-ALK in some cell lines and inhibited by it in others. In conclusion, our study makes the novel observation that signalling through NPM-ALK and JunB affect the expression of cytotoxic molecules in ALK+ ALCL. Moreover, these findings demonstrate the expression of GzB and Perforin in this lymphoma is not solely due its presumed CTL origin, but that oncogenic signalling is actively influencing the expression of these proteins.
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PMID:NPM-ALK and the JunB transcription factor regulate the expression of cytotoxic molecules in ALK-positive, anaplastic large cell lymphoma. 2132 8

Anaplastic lymphoma kinase-positive large B-cell lymphoma is a rare non-Hodgkin lymphoma that exhibits a characteristic immunoblastic/plasmablastic morphology and is frequently associated with t(2;17)(p23;q23) and expression of Clathrin-anaplastic lymphoma kinase fusion protein. Here, we report a refractory anaplastic lymphoma kinase-positive large B-cell lymphoma in a 49-year-old human immunodeficiency virus-positive man. The neoplastic cells expressed CD138, epithelial membrane antigen, CD45, and perforin, and showed a strong granular cytoplasmic anaplastic lymphoma kinase staining pattern. Conventional chromosome analysis revealed a clone with multiple anomalies and a chromosome count of 76 to 79. Fluorescence in situ hybridization studies showed 5 copies of the ALK gene with 2 intact signals and 3 signals resulting from 2 independent, previously unreported, rearrangements. One rearrangement, seen in 2 copies, involved translocation of ALK sequences to chromosome Xq21. The second rearrangement involved translocation of ALK sequences to chromosome 12q24.1. This case broadens the cytogenetic alterations in anaplastic lymphoma kinase-positive large B-cell lymphoma, and it also demonstrates the high genetic instability of this tumor.
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PMID:Anaplastic lymphoma kinase-positive large B-cell lymphoma with complex karyotype and novel ALK gene rearrangements. 2149 67

Anaplastic lymphoma kinase (ALK)-positive non-Hodgkin lymphoma (NHL) was long thought to be a disease occurring uniquely in T or null-cell lymphomas. More recently, however, a small number of B-lineage lymphomas have been reported to express ALK fusion genes. These tumors often exhibit a plasmablastic morphology, a finding which prompted our interest in looking for ALK fusions in plasma cell neoplasms. We studied 46 cases of extramedullary plasmacytoma by immunostaining with anti-ALK antibody and fluorescence in situ hybridization (FISH) analysis using an ALK break-apart probe and found one case to be ALK protein-positive and demonstrated the disruption of the ALK gene in this case. Immunohistochemistry showed that the tumor cells were strongly positive for CD138, VS38c, and epithelial membrane antigen, but lacked expression of CD20, CD79a, CD45, and CD30. Both RT-PCR and genomic DNA-PCR confirmed the CLTC-ALK fusion. This finding expands the lists of the ALK-positive tumors, and ALK-positive extramedullary plasmacytoma may benefit from the treatment of ALK inhibitor in the future.
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PMID:ALK-positive extramedullary plasmacytoma with expression of the CLTC-ALK fusion transcript. 2185 32

Anaplastic lymphoma kinase (ALK) has emerged as an important oncogene in a number of human malignancies ranging from non-Hodgkin lymphoma to neuroblastoma. In the former case, ALK is activated as a consequence of a chromosomal translocation and in the latter due to point mutations. In both cases the transforming potential of these oncogenic forms of ALK have been shown in vitro employing traditional cellular transformation assays including 3T3 foci formation. We reasoned that other ALK mutants which have been identified by the Cancer Genome Project may likewise possess transformation potential. We have selected seven ALK mutants identified in cell lines representative of a variety of human cancers based on position within the ALK protein, zygosity and frequency of detection including R1192Q, K1525E, C1021Y, R412C, A1252V, D1311A, K1518N and have compared their transformation capability in comparison to the published neuroblastoma-associated F1174L ALK mutant when expressed in immortalized p53(-/-) murine embryonic fibroblasts. Whilst the F1174L mutant reproducibly drives foci formation in vitro, the other ALK mutants fail in this task. Furthermore, apart from the F1174L ALK mutant, the ALK protein is not phosphorylated on tyrosine residue 1604 suggesting that they are kinase-inactive in this cellular context. We conclude that not all ALK mutants have transformation potential and may represent "passenger" mutations in the evolution of cancer.
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PMID:Assessment of the transforming potential of novel anaplastic lymphoma kinase point mutants. 2208 96

Anaplastic lymphoma kinase (ALK) was originally identified from a rare subtype of non-Hodgkin's lymphomas carrying t(2;5)(p23;q35) translocation, where ALK was constitutively activated as a result of a fusion with nucleophosmin (NPM). Aberrant ALK fusion proteins were also generated in inflammatory fibrosarcoma and a subset of non-small-cell lung cancers, and these proteins are implicated in their pathogenesis. Recently, ALK has been demonstrated to be constitutively activated by gene mutations and/or amplifications in sporadic as well as familial cases of neuroblastoma. Here we describe another mechanism of aberrant ALK activation observed in a neuroblastoma-derived cell line (NB-1), in which a short-form ALK protein (ALK(del2-3)) having a truncated extracellular domain is overexpressed because of amplification of an abnormal ALK gene that lacks exons 2 and 3. ALK(del2-3) was autophosphorylated in NB-1 cells as well as in ALK(del2-3)-transduced cells and exhibited enhanced in vitro kinase activity compared with the wild-type kinase. ALK(del2-3)-transduced NIH3T3 cells exhibited increased colony-forming capacity in soft agar and tumorigenicity in nude mice. RNAi-mediated ALK knockdown resulted in the growth suppression of ALK(del2-3)-expressing cells, arguing for the oncogenic role of this mutant. Our findings provide a novel insight into the mechanism of deregulation of the ALK kinase and its roles in neuroblastoma pathogenesis.
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PMID:Aberrant activation of ALK kinase by a novel truncated form ALK protein in neuroblastoma. 2224 60

Anaplastic lymphoma kinase-positive (ALK+) large B-cell lymphoma (LBCL) is a rare subtype of non-Hodgkin B-cell lymphoma that exhibits a more aggressive clinical course and poorer prognosis than the typical diffuse large B-cell lymphoma. In this study, we report the case of a 67-year-old man with left cervical lymph node swelling. Aspiration cytology revealed many clusters of cohesive, large, and solitary cells. The tumor cells had abundant cytoplasm and large round-to-oval nuclei with prominent nucleoli. The Giemsa staining specimens exhibited amorphous global bodies adjacent to some clusters. Histologically, large tumor cells occupied the lymph nodes in a sinusoidal pattern, and immunohistochemically, these cells were cytokeratin-, CD19(-), CD20(-), CD79a(-), CD3(-), CD30(-), CD138(+), IgG(-), IgA(+), and ALK(+). Chromogenic in situ hybridization revealed restricted immunoglobulin light-chain expression. Fluorescent in situ hybridization demonstrated translocation of the ALK gene. The tumor cells were negative for Epstein-Barr virus and human herpesvirus 8. It is important to differentiate ALK+LBCL from metastatic carcinoma and other lymphoma subtypes with similar histological features to ensure a proper treatment strategy and prediction of prognosis.
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PMID:A case of anaplastic lymphoma kinase-positive large B-cell lymphoma: aspiration cytology findings. 2345 5

Anaplastic lymphoma kinase positive, anaplastic large cell lymphoma (ALCL) is an uncommon T-cell non-Hodgkin lymphoma. A rare morphological variant-small cell variant of ALCL may pose diagnostic challenge especially when it presents primarily as a soft tissue mass. We present a rare case of small cell variant of ALCL in a 14-year-old female presented with arm swelling with emphasis on clinical, morphological and immunohistochemical aspects. Pathologists should be aware of this entity when considering a differential diagnosis of malignant round cell tumor as early and correct diagnosis has important clinical implications.
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PMID:Small cell variant of anaplastic large cell lymphoma presenting as arm mass in a child: a rare entity with diagnostic challenge. 2377 87


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