Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 70-year-old male was admitted because of anemia in September 1989, and primary myelofibrosis was diagnosed based on the presence of leukoerythroblastosis, a normal chromosomal analysis and pathological findings of fibrosis in bone marrow. Although he was anemic, he did not require any treatment for two years. Then his hematological status deteriorated to severe pancytopenia, and the marrow biopsy revealed marked hypoplasia with fatty replacement and scattered fibrosis. He was treated with metenolon without success and frequent transfusion of packed red cell was required. This hypoplastic status continued for seven months. In May 1992 his WBC count increased gradually with monocytosis. The marrow was filled with various stages of monocytes, with almost no fibrosis remaining. The chromosomal analysis was repeated but disclosed no abnormalities, consistent with the negative result of BCR-ABL rearrangement investigated by the RT-PCR method. One month later, when the patient died of multiple cerebral bleeding and infection, the leukocyte count exceed 90,000/microliters. It is known that major causes of death for patients with primary myelofibrosis are infection, bleeding, cardiac trouble and transformation to leukemia. We describe a case of myelofibrosis who developed to chronic myelomonocytic leukemia following severe aplastic phase.
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PMID:[Transformation into chronic myelomonocytic leukemia in a patient with primary myelofibrosis associated with severe hypoplasia: report of an autopsy case]. 778 40

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

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

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

Myeloproliferative neoplasms (MPNs) are traditionally separated into BCR-ABL-positive chronic myeloid leukemia (CML), and BCR-ABL-negative MPNs including primary myelofibrosis (PMF), essential thrombocythemia (ET), and so forth. One of the diagnostic requirements for PMF and ET is the absence of the Philadelphia chromosome, while its presence is almost universally indicative of CML. However, a diagnostic dilemma arises when Philadelphia chromosome-positive MPNs lack the majority of the typical features seen in CML. Some of these classic CML features include basophilIa, marked leukocytosis, neutrophils left-shift with myelocytes bulge, and "dwarf" megakaryocytes. Presented here is a case of a 32-year-old pregnant patient who did not have typical morphologic findings for CML, and yet the Philadelphia chromosome was positive. The patient demonstrated some pathologic features that are commonly presented in PMF that included bone marrow reticulin fibrosis, leukoerythroblastosis, splenomegaly, and increased serum lactate dehydrogenase.
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PMID:A case of Philadelphia chromosome positive myeloproliferative neoplasm in a pregnant woman with unusual primary myelofibrosis features. 2378 54

A 66-year-old male presented with fever and erythema at our hospital, and leukoerythroblastosis, anemia, thrombocytopenia, and multiple low-density lesions in the moderately enlarged spleen were detected. Skin tissue revealed CD8+ T cells with the expression of cytotoxic molecule markers involving fat lobules, and subcutaneous panniculitis T-cell lymphoma (SPTCL) was diagnosed. The bone marrow displayed no infiltration of lymphoid tumor cells, but hyperplasia of granulocytes and megakaryocytes with grade 2 stromal fibrosis. In addition, the bone marrow exhibited diffuse 18F-fluorodeoxyglucose (FDG) accumulation on FDG positron-emission tomography/computed tomography (FDG-PET/CT). Although chemotherapy improved SPTCL, the patient died from leukocytosis with leukoerythroblastosis. We obtained negative results for the JAK2 V617F mutation, and CD34+ cells were elevated in the bone marrow compared with the levels at initial examination. The final diagnosis was concurrent myelodysplastic syndrome (MDS) with fibrosis and SPTCL. This report highlights that it is essential to consider MDS or other myeloproliferative neoplasms (MPN) as possible complications when malignant lymphoma complicates myelofibrosis in the absence of bone marrow infiltration of lymphoma cells. Perhaps, the assessment of clonal markers of MPN and FDG accumulation patterns in the bone marrow by FDG-PET/CT could enable differentiation.
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PMID:[Concurrent subcutaneous panniculitis-like T-cell lymphoma and myelodysplastic syndrome with fibrosis]. 3116 97