Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The small cell and lymphohistiocytic variants of anaplastic large cell lymphoma are commonly misdiagnosed as reactive lymphadenopathies. A helpful histologic clue is the presence of perivascular cuffs of large lymphoid cells, and the diagnosis can be readily confirmed by immunostaining for CD30 and ALK. Int J Surg Pathol 8(2):153-156, 2000
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PMID:The Perivascular Cuff of Large Lymphoid Cells: A Clue to Diagnosis of Anaplastic Large Cell Lymphoma. 1149 80

The anaplastic lymphoma kinase (ALK) gene fuses to the nucleophosmin (NPM) gene as a result of a (2;5) translocation associated with a subtype of human lymphoma (initially designated anaplastic large cell lymphoma [ALCL] or Ki-1/CD30-positive lymphoma). The immunocytochemical detection of NPM-ALK (and proteins encoded by other ALK fusion genes) has allowed the definition of a tumor entity, "ALK-positive lymphoma" (which shows only partial overlap with pathologists' diagnosis of ALCL), to be defined and is invaluable in distinguishing this disease from ALK-negative large cell lymphomas. Eight variant ALK fusion proteins have been identified. Some are expressed only in ALCL, some are found only in the nonhematopoietic neoplasm inflammatory myofibroblastic tumor (IMT), and some are present in both types of malignancy. The ALK gene is silent in adult tissues except for restricted sites within the nervous system (consequently, patients with ALK-positive lymphoma produce antibodies to the ALK protein) but is expressed in some neuroblastomas and rhabdomyosarcomas. Biochemical studies suggest an anti-apoptotic function of NPM-ALK, and this may contribute to oncogenesis. Although ALK-positive lymphomas have a generally good prognosis, new therapeutic regimens are still needed for patients whose disease is refractory to conventional treatment.
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PMID:Anaplastic lymphoma kinase proteins and malignancy. 1156 Nov 61

Anaplastic large-cell lymphoma (ALCL) comprises a group of non-Hodgkin's lymphomas (NHLs) that were first described in 1985 by Stein and co-workers and are characterized by the expression of the CD30/Ki-1 antigen (Stein et al., 1985). Approximately half of these lymphomas are associated with a typical chromosomal translocation, t(2;5)(p23;q35). Much confusion about the exact classification and clinicopathological features of this subgroup of NHL was clarified with the identification of NPM-ALK (nucleophosmin-anaplastic lymphoma kinase) as the oncogene created by the t(2;5) (Morris et al., 1994). With the discovery of NPM-ALK as the specific lymphoma gene mutation, this NHL subtype could be redefined on the molecular level. This achievement was enhanced by the availability of specific antibodies that recognize ALK fusion proteins in paraffin-embedded lymphoma tissues. Several excellent recent reviews have summarized the histopathological and molecular findings of ALCL and their use in the classification of this lymphoma entity (Anagnostopoulos and Stein, 2000; Benharroch et al., 1998; Drexler et al., 2000; Foss et al., 2000; Gogusev and Nezelof, 1998; Kadin and Morris, 1998; Ladanyi, 1997; Morris et al., 2001; Shiota and Mori, 1996; Skinnider et al., 1999; Stein et al., 2000). This review will focus on the molecular function and signal transduction pathways activated by ALK fusion oncogenes, with recent advances and possible clinical implications to be discussed.
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PMID:Translocations involving anaplastic lymphoma kinase (ALK). 1160 14

In 1985, Stein et al demonstrated the expression of the lymphoid activation antigen CD30/Ki by neoplastic cells. Fifteen years after the first description, anaplastic large-cell lymphomas (ALCL) are now thought to be a heterogeneous group in terms of their clinical, morphologic, phenotypic, cytogenetic, and molecular biology features. However, on the basis of a specific genetic anomaly and expression of a chimeric nucleophosmin anaplastic lymphoma kinase (NPM-ALK) protein and its variants, a distinct clinicopathologic entity defined as "ALK-positive lymphoma" or "ALKoma" can be recognized. Based on molecular and clinical criteria, 3 entities of primary ALCL can be identified: primary systemic ALK positive, primary systemic ALK negative, and primary cutaneous ALCL. This review focuses on advances in the knowledge of primary systemic ALCL biology and discusses therapeutic approaches based on ALK expression. The presence of this protein appears to be an important prognostic factor and, combined with an age-adjusted International Prognostic Index, could allow researchers to design more specific clinical trials aimed at finding new, more efficacious and less toxic treatments.
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PMID:Primary systemic anaplastic large-cell lymphoma (CD30+): advances in biology and current therapeutic approaches. 1170 67

In cultures, and in tissues as well, Hodgkin's and Reed-Sternberg (H-RS) cells and anaplastic large cell lymphoma (ALCL) cells are known to express a variety of cytokines, including IL-1, -5, -6, -8, -9, TNF-alpha, GM-CSF, M-CSF, TGF-beta, CD70, CD80, and CD86. Various numbers of H-RS/ALCL cells may express cytokine receptors (R), such as CD30, CD40, IL-2R (CD25/CD122), IL-6R (CD126), IL-7R (CD127), TNF-R (CD120), TGF-beta-R (CD 105/endoglin), M-CSF-R (CD115), and SCF-R (CD117/c-kit receptor). All of these cytokines and cytokine receptors are implicated in the growth regulation of H-RS/ALCL cells, the histopathologic alterations in tissues, and the clinical manifestations in patients with Hodgkin's disease (HD) or ALCL. Many of these cytokines or cytokine receptors also play an important role in the pathogenesis of other types of lymphomas. In this review, we describe the cytokine or cytokine-receptor expression that is diacritic for H-RS/ALCL cells. The identification of such unique cytokine-cytokine receptor interactions is likely to explain the biologic property that distinguishes HD/ALCL from other types of lymphomas. These interactions include those of CD30L-CD30, CD40L-CD40, CD70-CD27, CD80/CD86- CD28, SCF-CD117, IL-9-IL-9R, and IL-7-IL-7R. The H-RS/ALCL cells express IL-9 and two cytokine receptors, CD30 and CD117, which are observed infrequently in NHLs. Although IL-7 expression is not restricted to H-RS/ALCL cells, the expression of IL-7 in conjunction with IL-9 and/or CD117 may be regarded as unique for HD/ALCL because of an unusual combination and a synergistic activity among these cytokines. The expression of CD70 and CD80/CD86 (as cytokines) may exert a unique effect in HD because of intimate contact between H-RS cells and CD27/CD28-positive T cells. The expression of these costimulators (CD70 and CD80/CD86) and other adhesion/constimulator molecules such as CD54 and CD58, along with the secretion of soluble cytokines such as IL-1, IL-6, IL-7, or TNFs by H-RS/ALCL cells, could result in the profound T-cell proliferation often seen in lymph nodes involved by HD and some ALCL. On the other hand, the expression of CD30L and CD40L by surrounding T cells may affect the proliferation of H-RS/ALCL cells. The cytokine-cytokine receptor interaction between H-RS cells and T cells via direct cell-cell contact is bidirectional, a situation not commonly seen in NHLs. Copyright 1995 S. Karger AG, Basel
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PMID:Hodgkin's Disease and Anaplastic Large Cell Lymphoma Revisited. 1. unique cytokine and cytokine receptor profile distinguished from that of non-hodgkin's lymphomas. 1172 67

Acquired chromosomal anomalies (most commonly translocations) in lymphoma and leukemia usually result in either activation of a quiescent gene (by means of immunoglobulin or T-cell-receptor promotors) and expression of an intact protein product, or creation of a fusion gene encoding a chimeric protein. This review summarizes current immunocytochemical studies of these 2 categories of oncogenic protein, with emphasis on the clinical relevance of their detection in diagnostic samples. Among the quiescent genes activated by rearrangement, expression of cyclin D1 (due to rearrangement of the CCND1 [BCL-1] gene) is a near-specific marker of t(11;14) in mantle cell lymphoma; BCL-2 expression distinguishes follicular lymphoma cells from their nonneoplastic counterparts in reactive germinal centers and appears to be an independent prognostic marker in diffuse large cell lymphoma; and TAL-1 (SCL) expression identifies T-cell acute lymphoblastic neoplasms in which this gene is activated. The protein products of other genes activated by chromosomal rearrangement have a role as markers of either lineage (eg, PAX-5 [B-cell-specific activator protein] for B cells, including B-lymphoblastic neoplasms), or maturation stage (eg, BCL-6 for germinal-center and activated B cells and MUM-1/IRF4 for plasma cells). Currently, no hybrid protein encoded by fusion genes is reliably detectable by antibodies recognizing unique junctional epitopes (ie, epitopes absent from the wild-type constituent proteins). Nevertheless, staining for promyelocytic leukemia (PML) protein will detect acute PML with t(15;17) because the microspeckled nuclear labeling pattern for PML-RARalpha is highly distinctive. Similarly, antibodies to the anaplastic lymphoma kinase (ALK) tyrosine kinase are valuable (because wild-type ALK is not found in normal lymphoid tissue) in detecting neoplasms (CD30-positive large T-cell lymphomas) with t(2;5) or its variants. Thus, immunocytochemical detection of the products of many rearranged genes in lymphoma and leukemia can be clinically informative and provide information on cellular and subcellular protein expression that cannot be inferred from studies based on messenger RNA.
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PMID:Proteins encoded by genes involved in chromosomal alterations in lymphoma and leukemia: clinical value of their detection by immunocytochemistry. 1178 Dec 20

The use of effective combination chemotherapy for all stages and subtypes of non-Hodgkin"s lymphoma (NHL) in children has resulted in a striking improvement in cure rates. Event-free survival now ranges from 70% to 90%, depending on the stage of disease and the NHL subtype. Risk-adapted therapy has resulted in a dramatic improvement in outcome for high-risk patients, at the cost of significantly increased short-term toxicity, and a reduction of therapy and toxicity for the lower-risk patient, while maintaining the excellent cure rate. Successful risk allocation of patients is dependent on the identification and continual validation of prognostic factors. The specific treatment protocol is the single most important factor predicting outcome today. Traditional prognostic factors such as stage and tumor burden are useful in selecting the intensity and length of therapy, rather than as a major indicator of likelihood of survival. In order to further improve cure rates and decrease toxicity, new biologic prognosticators need to be found and validated. Some promising avenues for study appear to be the presence or absence of adhesion molecules and of aberrant proteins that are specific to subtypes of lymphomas, such as soluble CD30 and anaplastic lymphoma kinase (ALK), the molecular classification of lymphomas on the basis of gene expression, and the evaluation of biologic markers for measuring early response to therapy.
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PMID:Pediatric non-Hodgkin's lymphoma: clinical and biologic prognostic factors and risk allocation. 1182 82

The t(2;5)(p23;q35) translocation results in the formation of a unique chimeric NPM-ALK protein (p80). Expression of this protein is considered to be one of the clinical features of anaplastic large cell lymphoma (ALCL). Recently recognized as one clinical subtype of ALCL, the small cell variant is prone to have a leukemic presentation. Although the small cell variant has been recognized as a subtype of ALCL, the clinical properties of this subtype, especially the immunophenotype of lymphoma cells in peripheral blood, have not yet been fully described. This report shows that neither CD30 nor p80 is detected by immunostaining in the predominant small cell malignant clone and also in large lymphoma cells in peripheral blood, while large cells and occasionally observed small cells in bone marrow were found to be positive for CD30 and p80. Our findings suggest that differential expression of CD30 and p80 between peripheral blood and bone marrow lymphoma cells is a property of the small cell variant of ALCL.
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PMID:CD30 and the NPM-ALK fusion protein (p80) are differentially expressed between peripheral blood and bone marrow in primary small cell variant of anaplastic large cell lymphoma. 1189 7

The sarcomatoid variant of anaplastic large cell lymphoma is one of the rarest histologic variants of this neoplasm. Due to its sarcomatoid features, it is frequently misdiagnosed as a poorly differentiated sarcoma, anaplastic carcinoma, or melanoma. We report the case of a 92-year-old woman with a sarcomatoid anaplastic large cell lymphoma mimicking a primary breast neoplasm. The patient presented with a rapidly enlarging lump in the left breast and nodules in the right axilla. The immunohistochemical profile showed reactivity for leukocyte common antigen, UCHL-1, vimentin, and CD30, but immunoexpression of anaplastic lymphoma kinase was lacking. Anaplastic large cell lymphomas are lymphoid neoplasms of T-cell/null-cell lineage that consistently express the activation marker CD30 and usually carry a gene rearrangement of the anaplastic lymphoma kinase gene. To the best of our knowledge, this is the first reported case of sarcomatoid anaplastic large cell lymphoma presenting as a primary breast neoplasm in which anaplastic lymphoma kinase expression was assessed.
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PMID:Sarcomatoid variant of anaplastic large cell lymphoma mimicking a primary breast cancer: a challenging diagnosis. 1203 65

Patients with relapsing Hodgkin's lymphoma (HL) have a rather poor prognosis and mechanisms that lead to resistance to therapy are poorly understood. Our aims were to investigate the immunohistochemical staining patterns of Rb (retinoblastoma protein) and the p53 tumour suppressor protein in HL at initial presentation and at relapse in order to elucidate a possible role in disease progression and resistance to therapy. Further to evaluate the presence and prognostic importance of Epstein-Barr virus (EBV) and anaplastic lymphoma kinase (ALK). Eighty-one cases of relapsing HL were reexamined histopathologically and immunostained for the expression of p53, Rb, ALK and CD30. EBV was detected with LMP-1 stainings and in situ hybridisation for EBER. Clinical data were extracted from the Swedish National Health Care Programme for HL. Median follow-up time was six years (range 0-12) from the date of relapse. The majority of cases were positive for p53 and Rb both at presentation and at relapse, though to a different extent. Both an increase and a decrease in the proportion of stained tumour cells were observed. None of our cases was ALK-positive and 44% were EBV-positive. No specific staining pattern was directly correlated to survival. In 12 patients a switch in HL subtype from diagnosis to relapse was observed and the five-year Hodgkin-specific survival (HLS) was statistically significantly inferior, 37 vs 81% (p = 0.002), in those patients. We found a significant relation between the expression of p53 and EBV at diagnosis and relapse, indicating a clonal relationship. We were unable to find any specific staining pattern of p53 or Rb, affecting survival.
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PMID:Relapsed Hodgkin's lymphoma: immunostaining patterns in relation to survival. 1215 93


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