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

The SL/Kh strain of mice spontaneously develop two types of non-thymic lymphomas at a high incidence and very short latency. The major type of lymphomas induce systemic lymph node enlargement and hepatosplenomegaly, and the minor type, proliferation predominantly in bone marrow often associated with spinal paralysis. Phenotypes of both types of lymphomas are indistinguishable: they express B220, 6C3, c-kit but not Thy-1.1, Mac-1 and surface Ig. In both types of lymphomas, the immunoglobulin heavy chain gene is found clonally rearranged in the order of VH-D-JH, whereas the light chain gene remains in germ line configuration. About half of the primary lymphomas are dual or oligoclonal in origin. R-PCR also demonstrates expression of lambda 5, RAG-1 and RAG-2, which are specifically associated with pre-B stage lymphocytes. All these observations indicate that both types of the SL/Kh lymphomas are pre-B-lymphomas.
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PMID:SL/KH strain of mice: a model of spontaneous pre-B-lymphomas. 832 39

A 35-year-old female presented in 1989 with hepatosplenomegaly, but no conclusive diagnosis was established. From 1992, she experienced transient episodes of facial flushing and palpitations. Osteosclerotic change was detected radiologically. Colonoscopy revealed massive polypoid lesions. Mast cells were demonstrated in bone marrow smear and imprinted preparations of colon biopsy specimens by toluidine blue staining. Plasma concentrations of histamine and soluble c-kit were elevated. She was successfully treated with interferon-alpha and prednisolone, resulting in the disappearance of histamine-related attacks and a gradual decrease in tumor size. However, the remission was interferon dose dependent. This case was considered as systemic mastocytosis with massive polypoid colon lesions and showed the importance of maintenance therapy with interferon-alpha.
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PMID:Systemic mastocytosis with extensive polypoid lesions in the intestines; successful treatment with interferon-alpha. 965 7

We describe the case of a 69-year-old man with systemic mastocytosis and severe osteopetrosis who carries a somatic activating mutation in the c-kit proto-oncogene. The patient initially presented with urticaria pigmentosa, progressing to systemic mast cell disease with severe anemia due to bone marrow involvement, chronic diarrhea, and hepatosplenomegaly. Direct sequencing using amplimers from reverse transcriptase-polymerase chain reactions (RT-PCR) from skin mast cell-derived RNA revealed a point mutation in the c-kit proto-oncogene at position 2468, introducing a new recognition site for the restriction endonuclease HinfI. Treatment with interferon-alpha 2a, prednisone, and erythropoietin was initiated. Subsequently, clinical symptoms improved significantly and hemoglobin levels are now stable at 13 g/dl.
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PMID:c-kit mutation and osteopetrosis-like osteopathy in a patient with systemic mast cell disease. 979 83

A 41-year-old woman presented with a 2-month history of pruritus and a generalized dermatitis that developed initially on the head and spread to the trunk, legs, and buttocks. The pruritus caused extreme discomfort and was not relieved by antihistamines or topical steroid treatment. The patient denied flushing, syncope, and vomiting. Her medical history included asthma treated with salmeterol/fluticasone propionate inhaler, and status post silicone breast augmentation. Physical examination revealed a papular dermatitis on the trunk and extremities composed of lesions up to 0.5 cm in diameter, surrounded by excoriation marks (Figure 1). There was no hepatosplenomegaly or lymphadenopathy. Darier's sign was negative. Results of complete blood count, peripheral blood film examination, and liver function tests were all with normal limits. A biopsy specimen taken from a lesion and stained with hematoxylin-eosin showed telangiectasias, with an increased number of mast cells around blood vessels (Figure 2). Positive Giemsa (Figure 3) and c-kit stain (Figure 4) indicated an increased number of mast cells. Bone marrow aspiration and total body CT performed to rule out systemic involvement showed no pathology. Protein electrophoresis was normal. Serum tryptase and histamine were within normal limits, and 24-hour urine collection for histamine was normal. Narrow-band UV-B treatment was begun 3 times weekly, reduced to twice weekly after 2 months, and then stopped. The first few treatments resulted in significant relief of the pruritus and regression of lesions. After 3 months without treatment, the patient remained free of pruritus and lesions.
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PMID:Telangiectasia macularis eruptiva perstans: unusual presentation and treatment. 1708

A 76-year old patient was referred to our Oncology Unit due to hepatosplenomegaly, anemia, thrombocytopenia, eosinophilia, elevation of lactat dehydrogenase and leucocytosis with occurrence of myeloid and erythroid precursors in the peripheral blood. Histopathological examination of the bone marrow and molecular genetics showing a c-kit-D816V-mutation confirmed the diagnosis of systemic mastocytosis without evidence of idiopathic myelofibrosis. After starting of prednisone treatment anemia, thromocytopenia and the patient's performance status rapidly improved.
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PMID:[76-year old patient with suspected but not confirmed "idiopathic myelofibrosis"]. 2187 49

As leukemic transformation of myeloproliferative neoplasms (MPNs) worsens the clinical outcome, reducing the inherent risk of the critical event in MPN cases could be beneficial. Among genetic alterations concerning the transformation, the frequent one is TP53 mutation. Here we show that retroviral overexpression of Jak2 V617F mutant into wild-type p53 murine bone marrow cells induced polycythemia vera (PV) in the recipient mice, whereas Jak2 V617F-transduced p53-null mice developed lethal leukemia after the preceding PV phase. The leukemic mice had severe anemia, hepatosplenomegaly, pulmonary hemorrhage and expansion of dysplastic erythroid progenitors. Primitive leukemia cells (c-kit+Sca1+Lin- (KSL) and CD34-CD16/32-c-kit+Sca1-Lin- (megakaryocyte-erythroid progenitor; MEP)) and erythroid progenitors (CD71+) from Jak2 V617F-transduced p53-null leukemic mice had leukemia-initiating capacity, however, myeloid differentiated populations (Mac-1+) could not recapitulate the disease. Interestingly, recipients transplanted with CD71+ cells rapidly developed erythroid leukemia, which was in sharp contrast to leukemic KSL cells to cause lethal leukemia after the polycythemic state. The leukemic CD71+ cells were more sensitive to INCB18424, a potent JAK inhibitor, than KSL cells. p53 restoration could ameliorate Jak2 V617F-transduced p53-null erythroleukemia. Taken together, our results show that p53 loss is sufficient for inducing leukemic transformation in Jak2 V617F-positive MPN.
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PMID:Loss of p53 induces leukemic transformation in a murine model of Jak2 V617F-driven polycythemia vera. 2806 30