Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Common Variable Immunodeficiency (CVID) and agammaglobulinemia are two of the main types of symptomatic primary antibody deficiencies. The pathogenic origins of these two diseases are different; agammaglobulinemia is a group of inherited disorders that usually are caused by mutations in the gene encoding Bruton Tyrosine Kinase (BTK) protein while CVID is a heterogeneous disorder mainly without monogenic cause. However, both diseases share a characteristic of frequent bacterial infections, a decline in serum immunoglobulin levels, and abnormality in antibody responses. The demographics and immunologic parameters, clinical manifestation, and mortality statistics from 297 patients with CVID and agammaglobulinemia followed up over 2 decades in the Children's Medical Center of Iran. Age at onset of symptom in agammaglobulinemia was earlier than CVID but the course of disease in CVID patients was longer than agammaglobulinemia patients. Pulmonary infections were the most prevalent clinical manifestations in both groups of patients. Lymphadenopathy, hepatomegaly, and splenomegaly were significantly higher in CVID patients than agammaglobulinemia patients and there was a significant association between these complications and mortality in CVID patients. Among 297 patients, 128 patients (88 CVID and 40 agammaglobulinemia) deceased. The predominant causes of death in CVID patients were infections, chronic lung disease, and malignancy while in agammaglobulinemia patients were infections and respiratory failure. Infections, especially respiratory infections were the most common complication and cause of death in both CVID and agammaglobulinemia groups and recent treatment advances even Immunoglobulin replacement cannot completely control these complications. Thus prompt recognition and specific management of these complications are worthwhile.
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PMID:Comparison of clinical and immunological features and mortality in common variable immunodeficiency and agammaglobulinemia patients. 3105 34

Deletion of long arm of chromosome 20 [del(20q)] is the second most frequent recurrent chromosomal abnormality in hematological malignancies. It is detected in 10% of myeloproliferative neoplasms, 4-5% of myelodysplastic syndromes, and 1-2% of acute myeloid leukaemia. Recurrent, non-random occurrence of del(20q) indicates that it is a pathogenic driver in myeloid malignancies. Genetic mapping of patient samples has identified two regions of interest on 20q - the "Common Deleted Region" (CDR) and "Common Retained Region" (CRR), which was often amplified. We proposed that the CDR contained tumor suppressor gene(s) (TSG) and the CRR harbored oncogene(s); loss of a TSG together with over-expression of an oncogene favored development of myeloid malignancies. Protein Tyrosine Phosphatase Receptor T (PTPRT) and Hemopoietic cell kinase (HCK) were identified to be the likely candidate TSG and oncogene respectively. Retroviral transduction of HCK into PTPRT-null murine LKS+ stem and progenitor cells resulted in hyperproliferation in colony forming assays and hyperphosphorylation of intracellular STAT3. Furthermore, over half of the murine recipients of these transduced cells developed erythroid hyperplasia, polycythemia and splenomegaly at 12 months, although no leukemic phenotype was observed. The findings suggested that HCK amplification coupled with PTPRT loss in del(20q) leads to development of a myeloproliferative phenotype.
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PMID:Hemopoietic Cell Kinase amplification with Protein Tyrosine Phosphatase Receptor T depletion leads to polycythemia, aberrant marrow erythoid maturation, and splenomegaly. 3106 22

Deregulated activation of the latent transcription factor STAT3 has been implicated in the pathogenesis of myeloproliferative and lymphoproliferative hematologic disorders. The uncontrolled activation of STAT3 has traditionally been assigned to its elevated phosphorylation at tyrosine 705 (pY705) and associated nuclear transcriptional activity. By contrast, a transcriptional role for serine 727 phosphorylation (pS727) of STAT3 has recently emerged, suggesting that pS727 may account for the pathological activity of STAT3 in certain disease settings. Here, by coupling pS727-STAT3-deficient Stat3SA/SA mice with a STAT3-driven mouse model (gp130F/F) for myeloproliferative and lymphoproliferative pathologies, we reveal a key role for pS727-STAT3 in promoting multiple hematologic pathologies. The genetic blockade of pS727-STAT3 in gp130F/F:Stat3SA/SA mice ameliorated the neutrophilia, thrombocytosis, splenomegaly and lymphadenopathy that are features of gp130F/F mice. The protection against thrombocytosis in gp130F/F:Stat3SA/SA mice coincided with normalized megakaryopoiesis in both bone marrow and spleen compartments. Interestingly, pS727-STAT3-mediated abnormal lymphopoiesis in gp130F/F mice was more pronounced in lymph nodes compared to thymus, and was characterized by elevated numbers of B cells at the expense of T cells. Furthermore, pS727-STAT3 dependency for these hematologic pathologies coincided with transcriptional activity on STAT3-regulated genes, rather than its effect on mitochondrial and metabolic genes. Collectively, these findings suggest that pS727 plays a critical pathological role in modulating the transcriptional activity of STAT3 in hematologic disorders.
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PMID:STAT3-driven hematopoiesis and lymphopoiesis abnormalities are dependent on serine phosphorylation. 3220 Feb 65


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