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)

A 60-year-old Japanese woman was admitted to our hospital because of fatigue, weight loss and abdominal distension. Myelofibrosis was diagnosed, based on anemia, huge hepatosplenomegaly, leukoerythroblastosis and bone marrow fibrosis. Following treatment with ranimustine, anemia and splenomegaly improved. Seven months after initial therapy of ranimustine, however, polycythemia (RBC 7.39 x 10(6)/microliter; Hb 19.1 g/dl, Ht 65.9%) developed gradually, then RBC decreased to normal level following venesection (total 1,200 ml). After 32 months, blastic transformation occurred. The blasts were negative for myeloperoxidase. By flow cytometric analysis, the cells were positive for CD2, CD13, CD33 and HLA DR. Thus, AML (M0) was diagnosed. Despite of treatment with multicytotoxic agents, she died of DIC 36 months after the initial diagnosis of myelofibrosis. The progression from myelofibrosis to polycythemia is rare and only 15 cases have been reported so far. In addition, although a chromosomal abnormality, 46, XX, t(3; 12) (q25; p11), was present at the time of first diagnosis of myelofibrosis, the development of an additional abnormality, del(11) (q-), might be related to the transformation to AML.
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PMID:[A case of myelofibrosis that developed polycythemia vera following treatment with ranimustine and then acute myelogenous leukemia (M0)]. 882 83

Cbfa1, a transcriptional factor that belongs to the runt-domain gene family, plays a pivotal role in osteogenesis. Cbfa1-deficient mice completely lacked both intramembranous and endochondral bone formation owing to the maturational arrest of osteoblasts, resulting in a total lack of bone marrow throughout the entire skeleton. To investigate the development of hematopoiesis in Cbfa1-deficient mice, hematopoietic tissues and peripheral blood were examined. Colony-forming assays of yolk sac at embryonic day 10.5 (E10.5) and liver at E12.5 showed normal numbers of hematopoietic precursors in the mutant embryos. Further, histological examination and flow-cytometric analysis showed normal hematopoietic development of liver and spleen in the mutant embryos until E17.5. However, mutant embryos at E18.5 showed large hematopoietic foci in the periportal area of liver and mild splenomegaly with dilated vessels, and an increase of myeloid cells was observed in both organs. Flow-cytometric analysis also demonstrated a relative increase of granulocytes and a relative decrease of B-cells reciprocally in the livers and spleens of the mutant embryos. Colony-forming assays showed that the frequency of colony-forming unit-culture (CFU-C) was elevated in liver, and both the frequency and total number of CFU-C were increased in spleen of mutant embryos at E18.5. Moreover, leukoerythroblastosis was observed in peripheral blood of the mutant embryos. These data demonstrate that the congenital lack of bone marrow caused excessive levels of extramedullary hematopoiesis in both liver and spleen at the late embryonic stage.
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PMID:Excessive extramedullary hematopoiesis in Cbfa1-deficient mice with a congenital lack of bone marrow. 1004 12

Myelofibrosis is characterized by reticulin fibrosis of the bone marrow with resulting features of myelophthisis. Besides hematopoietic malignancies and other neoplasms involving the bone marrow, myelofibrosis has been described in association with autoimmune disorders, especially systemic lupus erythematosus. We describe the clinicopathologic features of a primary form of autoimmune myelofibrosis (AIMF) in patients who do not have systemic lupus erythematosus or another well-defined autoimmune syndrome. Absence of marked splenomegaly, peripheral blood cytopenias with mild teardrop poikilocytosis and leukoerythroblastosis, bone marrow lymphoid aggregates, and presence of autoantibodies are some of the salient features of primary AIMF. AIMF should especially be differentiated from chronic idiopathic myelofibrosis, a neoplastic myeloproliferative disease. Primary AIMF appears to have an excellent prognosis, with all patients reported in this series responding to a short course of corticosteroid therapy.
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PMID:Primary autoimmune myelofibrosis: definition of a distinct clinicopathologic syndrome. 1250 61

We report on a 58-year-old male diagnosed as having primary myelofibrosis with thrombocytopenia, who died of fatal septic shock and rhabdomyolysis after platelet concentrates (PCs) transfusion. The initial diagnosis of primary myelofibrosis was established by splenomegaly, leukoerythroblastosis and bone marrow fibrosis. PCs were transfused because of thrombocytopenia with marked bleeding tendency. Soon after the PCs transfusion in March 2000, he had attacks of chest pain, back pain and myalgia, then went into shock and died of unknown causes. PCs were suspected as being the cause of death, because Streptococcus pneumoniae was found in the culture of PCs in the WBC-reduction in-line filter and fresh frozen plasma from the same donor preserved in the Japan Red Cross Center. Rhabdomyolysis, neutrophil infiltration and phagocytosed bacteria were found from the autopsy materials, which were identified by DNA analysis as the same species found in the PCs. PCs are kept at room temperature because platelet function is lost in the cold. When PCs are contaminated with bacteria, marked multiplication induces fatal bacteremia. This is a rare report in Japan of fatal septic shock caused by PCs with bacterial contamination. We must pay strict attention to bacterial contamination in blood components.
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PMID:[Fatal septic shock and rhabdomyolysis following transfusion of platelet concentrates contaminated with Streptococcus pneumoniae]. 1288 16

Idiopathic myelofibrosis, a chronic myeloproliferative disorder of unknown origin, is characterized by splenomegaly, extramedullary hematopoiesis, leukoerythroblastosis, teardrop erythrocytes, and myelofibrosis. It is a rare disorder in childhood. The authors describe a 4-year-old girl with features consistent with idiopathic myelofibrosis, who also had generalized solid laminated periosteal reaction involving all long bones. The presence of thrombocytopenia at the onset and lack of leukocytosis were in contrast to the reported features seen in children. Recent case reports describe a relatively indolent course in children. Spontaneous remissions have also been described in pediatric cases. The fulminant course of this patient without any features of malignant transformation was noteworthy in this regard.
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PMID:Idiopathic myelofibrosis with generalized periostitis in a 4-year-old girl. 1589 65

We present results of 2 similarly designed but separate phase 2 studies involving single-agent lenalidomide (CC-5013, Revlimid) in a total of 68 patients with symptomatic myelofibrosis with myeloid metaplasia (MMM). Protocol treatment consisted of oral lenalidomide at 10 mg/d (5 mg/d if baseline platelet count < 100 x 10(9)/L) for 3 to 4 months with a plan to continue treatment for either 3 or 24 additional months, in case of response. Overall response rates were 22% for anemia, 33% for splenomegaly, and 50% for thrombocytopenia. Response in anemia was deemed impressive in 8 patients whose hemoglobin level normalized from a baseline of either transfusion dependency or hemoglobin level lower than 100 g/L. Additional treatment effects in these patients included resolution of leukoerythroblastosis (4 patients), a decrease in medullary fibrosis and angiogenesis (2 patients), and del(5)(q13q33) cytogenetic remission accompanied by a reduction in JAK2(V617F) mutation burden (1 patient). Grade 3 or 4 adverse events included neutropenia (31%) and thrombocytopenia (19%). We conclude that lenalidomide engenders an intriguing treatment activity in a subset of patients with MMM that includes an unprecedented effect on peripheral blood and bone marrow abnormalities.
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PMID:Lenalidomide therapy in myelofibrosis with myeloid metaplasia. 1660 64

Deficiency of vitamin B12 is a well known cause of megaloblastic anemia and pancytopenia. Splenomegaly and leukoerythroblastosis are much less well known manifestations of B12 deficiency. We report a B12 deficient female with severe pancytopenia including normocytic anemia who also had enlarged spleen and circulating nucleated red blood cells as well as circulating immature myeloid cells. Although these findings are reported in the earlier literature, more modern reviews of the subject often fail to mention this association. We review the literature on these unusual manifestations of B12 deficiency and remind clinicians that splenomegaly and erythroblastosis can serve as diagnostic clues in cases of severe megaloblastic anemia secondary to B12 deficiency.
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PMID:Severe vitamin B12 deficiency resulting in pancytopenia, splenomegaly and leukoerythroblastosis. 1822 85

Primary myelofibrosis (PMF) is a clonal stem cell disorder that manifests clinically as anemia, splenomegaly due to extramedullary hematopoiesis, leukoerythroblastosis, and constitutional symptoms, which are the clinical hallmarks of PMF. Within the past three years it has been determined that a single, recurrent, somatic mutation in the gene encoding the cytoplasmic tyrosine kinase Janus kinase 2 (JAK2) occurs in the majority of patients with PMF, and more recently, activating mutations in the gene encoding the thrombopoietin receptor MPL have also been identified in a subset of PMF patients. These discoveries have yielded important insights into the pathogenesis of PMF and have brought about the first opportunity for rationally targeted therapy for this disorder. Here we present an updated review of the pathogenesis, definition, and treatment of PMF in light of the discovery of JAK2 and MPL mutations, as well as other recent work in the myeloproliferative neoplasm field.
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PMID:Primary myelofibrosis: update on definition, pathogenesis, and treatment. 1894 94

Primary myelofibrosis (PMF) is a chronic myeloproliferative neoplasm characterized by progressive anemia, massive splenomegaly, leukoerythroblastosis, extramedullary hematopoiesis and in about 50% of cases the presence of JAK2V617F mutation. Curative therapy in PMF is currently possible only with allogeneic haematopoietic stem cell transplantation which is, unfortunately, associated with relatively high risks of mortality and morbidity which undermine its broad applications. Non-transplant treatment modalities are used for palliative purposes. Recently, anti-angiogenic drugs such as thalidomide have been used to treat these patients on the basis of the prominent bone marrow angiogenesis. Here, we report the case of a patient suffering from JAK2V617F-positive PMF with marked bone marrow neo-angiogenesis. The patient was treated with thalidomide but after 20 days developed life-threatening toxic epidermal necrolysis (TEN). To the best of our knowledge this is the first case of TEN in a patient with PMF under thalidomide therapy.
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PMID:Toxic epidermal necrolysis in a patient with primary myelofibrosis receiving thalidomide therapy. 1905 92

Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm that involves primarily the megakaryocytic lineage. After many years, a few patients with ET may develop bone marrow (BM) fibrosis and rarely develop osteosclerosis. A 60-yr-old female was admitted due to severe left upper quadrant abdominal discomfort. She had been diagnosed as ET 19 yrs ago. On liver computed tomography severe splenomegaly was shown. Laboratory tests revealed WBC 24.3x10(9)/L, hemoglobin 13.4 g/dL, platelets 432x10(9)/L, lactate dehydrogenase 4,065 IU/L (reference range; 240-480). Blood smear demonstrated leukoerythroblastosis, teardrop cells, and giant and hypogranular platelets. BM study revealed inadequate aspirate due to dry tap. BM biopsy showed clusters of dysplastic megakaryocytes, grade 3 fibrosis, and severe osteosclerosis. Major/minor BCR-ABL1 rearrangement and JAK2 V617F mutation were not detected. Cytogenetic studies revealed normal karyotype. According to the 2008 WHO diagnostic criteria, the patient was diagnosed as having post-essential thrombocythemia myelofibrosis with severe osteosclerosis.
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PMID:[A case of post-essential thrombocythemia myelofibrosis with severe osteosclerosis]. 2044 28


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