Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019214 (hepatosplenomegaly)
 4,408 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A transgenic mouse strain with the zeta-globin promoter and the vHa-ras oncogene develops an array of mesenchymal and epithelial neoplasms described here. The predominate mesenchymal tumors were dermal spindle cell tumors, which resembled malignant fibrous histiocytomas found in humans. They were associated with hepatosplenomegaly and developed beneath squamous papillomas. The hepatosplenomegaly was associated with infiltrates of cells that tended toward myelocytic or monocytic differentiation. Other epithelial tumors included keratoacanthomas and squamous cell carcinomas. Squamous cysts, some with squamous cell carcinomas, of the salivary glands and mammary carcinomas were also found. Odontogenic tumors, which sometimes differentiated into ameloblastomas, were one of the more unusual tumor types observed. Other, less frequent tumors were also noted. The tumors described here are a potentially valuable experimental resource that may lead to an understanding of malignant fibrous histiocytoma-like lesions, odontogenic tumors, and tumor progression.
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PMID:Multiple tumor types appear in a transgenic mouse with the ras oncogene. 847 93

We present a case of a 17-year old patient with extreme hepatosplenomegaly, hyperthrombocytosis, hyperleucocytosis and the presence of myelo- and megakaryoblasts in the peripheral blood film. Numerous complications that occurred in the course of the disease made cytostatic treatment difficult. Since Ph chromosome and hybrid gene bcr/abl were absent, the diagnosis of unclassified chronic myeloproliferative syndrome in the phase of blast crisis was established. Immunophenotyping confirmed a mixed myelo- megakaryoblastic character of the crisis. In the differential diagnosis other myeloproliferative syndromes were taken into account including i(17q) syndrome. The patient died after a 13-month observation due to neoplasm progression and sepsis.
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PMID:[Unclassified chronic myeloproliferative Ph(-); i(17q); +8 syndrome with mixed myelo-megakaryoblastic crisis--case report]. 862 49

In chronic myeloid leukemia (CML), the BCR-ABL fusion oncoprotein activates multiple pathways involved in cell survival, growth promotion and disease progression. In this report, we show that the signal-transducing adaptor protein-2 (STAP-2) is involved in BCR-ABL activity. We demonstrate that STAP-2 bound to BCR-ABL, and BCR and ABL proteins, depending on the STAP-2 Src homology 2-like domain. BCR-ABL phosphorylates STAP-2 Tyr250 and the phosphorylated STAP-2 in turn upregulated BCR-ABL phosphorylation, leading to enhanced activation of downstream signaling molecules including ERK (extracellular-signal-regulated kinase), STAT5 (signal transducer and activator of transcription 5), BCL-xL (B-cell lymphoma-extra large) and BCL-2(B-cell lymphoma 2). In addition, STAP-2 interacts with BCR-ABL to alter chemokine receptor expression leading to downregulation of CXCR4 and upregulation of CCR7. The interaction between STAP-2 and BCR-ABL plays a crucial role in conferring a growth advantage and resistance to imatinib, a BCR-ABL inhibitor, as well as tumor progression. Notably, mice injected with BCR-ABL/STAP-2-expressing Ba/F3 cells developed lymph node enlargement and hepatosplenomegaly. Moreover, suppression of STAP-2 in K562 CML cells resulted in no tumor formation in mice. Our results demonstrate a critical contribution of STAP-2 in BCR-ABL activity, and suggest that STAP-2 might be an important candidate for drug development for patients with CML. Furthermore, the expression of STAP-2 provides useful information for estimating the characteristics of individual CML clones.
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PMID:STAP-2 interacts with and modulates BCR-ABL-mediated tumorigenesis. 2223 45

An infant presented with fever and purulent discharge from the left ear, proptosis of the right eye, and hepatosplenomegaly. She was diagnosed with acute monoblastic leukemia on morphological and flowcytometric analysis of the bone marrow. Karyotyping showed a jumping translocation (JT) involving the long arm of chromosome 1 as the sole cytogenetic abnormality in 29 metaphases. The patient died within 2 months of diagnosis. The presence of JT in a de novo infant AML as a sole cytogenetic abnormality indicates its possible role in leukemogenesis unlike previous reports that have implicated its role in tumor progression only.
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PMID:Jumping translocation in a case of de novo infant acute myeloid leukemia. 2401 27