Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mast cells (MC) are multipotent hemopoietic effector cells producing diverse mediators like histamine, heparin, or tissue type plasminogen activator. We report a 75-year-old male patient with myelodysplastic syndrome (MDS) of recent onset (3 months' history) associated with a massive leukemic spread of immature tryptase+ MC (tentative term: myelomastocytic leukemia). The patient presented with pancytopenia, bleeding, hypofibrinogenemia, and an increased cellular tryptase level. Moreover, an excessive elevation of plasmin-antiplasmin complexes (9,200 ng/ml; normal range: 10-150), an elevated D-dimer, and an increase in thrombin-antithrombin III complexes were found. The identity of the circulating MC was confirmed by immunophenotyping (CD117/c-kit+, CD123/IL-3R alpha-, CD11b/C3biR-), biochemical analysis (cellular ratio [ng:ng] of tryptase to histamine >1), and electron microscopy. Bone marrow (bm) examination showed trilineage dysplasia (17% blasts), 30% diffusely scattered MC, and a complex karyotype. No dense, compact MC infiltrates (mastocytosis) were detectable in bm sections. Despite hyperfibrinolysis and mediator syndrome (flushing, headache), the patient received remission induction polychemotherapy (DAV) followed by two cycles of consolidation with intermediate dose ARA-C (2 x 1 g/m2/day on days 1, 3, and 5). He entered complete remission after the first chemotherapy cycle without evidence of recurring MDS. Moreover, in response to chemotherapy, the hyperfibrinolysis and mediator syndrome resolved, and the circulating c-kit+ MC disappeared. We suggest consideration of polychemotherapy as a therapeutic option in patients with high-risk MDS of recent onset, even in the case of MC lineage involvement.
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PMID:Hyperfibrinolysis in a case of myelodysplastic syndrome with leukemic spread of mast cells. 1033 14

Mast cell leukemia (MCL) is a life-threatening disease associated with high mortality and drug-resistance. Only few patients survive more than 12 months. We report on a 55-year-old female patient with acute MCL diagnosed in May 2012. The disease was characterized by a rapid increase in white blood cells and mast cells (MC) in the peripheral blood, and a rapid increase of serum tryptase levels. The KIT D816H mutation was detected in the blood and bone marrow (BM). Induction chemotherapy with high-dose ARA-C and fludarabine (FLAG) was administered. Unexpectedly, the patient entered a hematologic remission with almost complete disappearance of neoplastic MC and a decrease of serum tryptase levels to normal range after 2 cycles of FLAG. Consecutively, the patient was prepared for allogeneic stem cell transplantation. However, shortly after the third cycle of FLAG, tryptase levels increased again, immature MC appeared in the blood, and the patient died from cerebral bleeding. Together, this case shows that intensive chemotherapy regimens, like FLAG, may induce remission in acute MCL. However, treatment responses are short-lived and the overall outcome remains dismal in these patients. We propose to separate this acute type of MCL from more subacute or chronic variants of MCL.
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PMID:FLAG-induced remission in a patient with acute mast cell leukemia (MCL) exhibiting t(7;10)(q22;q26) and KIT D816H. 2459 74