Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutations in the genes of hematopoietic growth factor receptors as a cause of congenital cytopenia, such as congenital amegakaryocytic thrombocytopenia (CAMT) or severe congenital neutropenia (CN), are discussed. There are striking differences in the relevance of receptor mutations in these diseases. CAMT is a rare disease characterized by severe hypomegakaryocytic thrombocytopenia during the first years of life that develops into pancytopenia in later childhood. In patients with CAMT, we found inherited mutations in c-mpl, the gene coding for the thrombopoietin receptor, in 8 out of 8 cases. The type of mutation seems to correlate with the clinical course seen in the patients. Functional studies demonstrated defective thrombopoietin (TPO) reactivity in hematopoietic progenitor cells and platelets in CAMT patients. CN is a group of hematopoietic disorders characterized by profound, absolute neutropenia due to a maturation arrest of myeloid progenitor cells. About 10% of all patients develop secondary MDS/leukemia. The malignant progression is associated with acquired nonsense mutations within the G-CSF receptor gene that lead to the truncation of the carboxy-terminal cytoplasmic domain of the receptor protein involved in maturation of myeloid progenitor cells. This seems to be one important step in leukemogenesis in CN patients. CAMT is caused by inherited mutations in c-mpl, the gene for the thrombopoietin receptor, which lead to reduced or absent reactivity to TPO. In contrast, mutations in the G-CSF receptor in CN are acquired and are most probably connected with progression of the neutropenia into MDS/leukemia as a result of a loss of differentiation signaling.
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PMID:Implications of mutations in hematopoietic growth factor receptor genes in congenital cytopenias. 1145 19

Molecular targeting of novel therapies has the promise of inducing very specific biologic effects. In clinical hematology and oncology, molecular targeting of specific cell surface receptors with erythropoietin, G-CSF, or GM-CSF has been used to stimulate erythropoiesis and granulopoiesis, respectively. Although anemia and neutropenia can be corrected with targeted therapy, safe and effective treatment of thrombocytopenia remains an unmet medical need. While platelet transfusions still represent the standard of care for severe thrombocytopenia, there are several negative aspects associated with their use, including issues of availability, transient effectiveness, costs, adverse effects, negative perception by patients, and infection considerations. Despite extensive investigations of cytokines which act primarily on primitive levels of hematopoiesis, pharmacologic interventions to date have failed to elevate platelet counts in a reliable, highly effective, and well-tolerated fashion. Recombinant human interleukin-11 has been approved by the U.S. Food and Drug Administration for the treatment of chemotherapy-induced thrombocytopenia but has only modest efficacy and significant side effects. The identification of c-Mpl as the thrombopoietin receptor has opened new avenues for the therapeutic manipulation of thrombopoiesis. The development of specific c-Mpl ligands, including recombinant human thrombopoietin (rHuTPO), has allowed investigators to target this receptor for the treatment of chemotherapy-induced thrombocytopenia and other medical disorders characterized by extremely low platelet counts. As a potent stimulator of platelet production, rHuTPO has the potential to reduce the need for platelet transfusions and their attendant complications.
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PMID:Targeted approaches for the treatment of thrombocytopenia. 1170 Mar 88

Autoantibodies reduce the life span of platelets, granulocytes, and red blood cells. This may result in thrombocytopenia with bleeding, in neutropenia with infection, and in anemia, respectively. Immune-hemocytopenias can manifest as primary disease without another cause, or they are associated with other underlying morbidities such as autoimmune diseases, lymphoproliferative diseases, immune defects, or viral infections. Diagnosis is confirmed by laboratory tests showing autoantibodies against the respective blood cells. Indication for treatment is the clinical manifestation of symptoms: bleeding in autoimmune thrombocytopenia, infections in neutropenia, and symptomatic anemia, respectively. Especially in case of thrombocytopenia patients should not be treated because of abnormal laboratory values, only. To date steroids are the basic treatment in autoimmune thrombocytopenia and hemolytic anemia, while prophylactic antibiotics are the main treatment in autoimmune neutropenia. Growth factors like the new thrombopoietin receptor agnonists in autoimmune thrombocytopenia or G-CSF in autoimmune neutropenia, and anti-CD20 antibodies are new options for treatment.
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PMID:[Autoimmune thrombocytopenia, neutropenia and hemolysis]. 1922 48

Eltrombopag is a non-peptide thrombopoietin receptor agonist. Eltrombopag has originally been developed for conditions where therapy for thrombocytopenia is needed. Secondary to eltrombopag have been reported thrombotic events, chest pain, acute renal failure, neutropenia, ascites, retinal exudates, antiphospholipid syndrome. In this case, we present a 53 year-old patient who had diagnosis of Idiopathic Thrombocytopenic Purpura (ITP) for 30 years with splenectomy. He's still having low thrombocyte counts despite the classical ITP therapy. He was treated with eltrombopag for the last 2 months and had inferior myocardial infarction despite that having no additional risk factors for coronary heart disease.
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PMID:Eltrombopag Induced Thrombosis: A Case with Acute Myocardial Infarction. 2656 Apr 93

Selinexor is an oral, small molecule inhibitor of the nuclear export protein exportin 1 with demonstrated activity in hematologic and solid malignancies. Side effects associated with selinexor include nausea, vomiting, fatigue, diarrhea, decreased appetite, weight loss, thrombocytopenia, neutropenia, and hyponatremia. We reviewed 437 patients with multiple myeloma treated with selinexor and assessed the kinetics of adverse events and impact of supportive care measures. Selinexor reduced both platelets and neutrophils over the first cycle of treatment and reached a nadir between 28 and 42 days. Platelet transfusions and thrombopoietin receptor agonists were effective at treating thrombocytopenia, and granulocyte colony stimulating factors were effective at resolving neutropenia. The onset of gastrointestinal side effects (nausea, vomiting, and diarrhea) was most common during the first 1-2 weeks of treatment. Nausea could be mitigated with 5-HT3 antagonists and either neurokinin 1 receptor antagonists, olanzapine, or cannbainoids. Loperamide and bismuth subsalicylate ameliorated diarrhea. The primary constitutional side effects of fatigue and decreased appetite could be managed with methylphenidate, megestrol, cannabinoids or olanzapine, respectively. Hyponatremia was highly responsive to sodium replacement. Selinexor has well-established adverse effects that mainly occur within the first 8 weeks of treatment, are reversible, and respond to supportive care.
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PMID:Integrated safety profile of selinexor in multiple myeloma: experience from 437 patients enrolled in clinical trials. 3209 61

Evans' syndrome (ES) is defined as the concomitant or sequential association of warm auto-immune haemolytic anaemia (AIHA) with immune thrombocytopenia (ITP), and less frequently autoimmune neutropenia. ES is a rare situation that represents up to 7% of AIHA and around 2% of ITP. When AIHA and ITP occurred concomitantly, the diagnosis procedure must rule out differential diagnoses such as thrombotic microangiopathies, anaemia due to bleedings complicating ITP, vitamin deficiencies, myelodysplastic syndromes, paroxysmal nocturnal haemoglobinuria, or specific conditions like HELLP when occurring during pregnancy. As for isolated auto-immune cytopenia (AIC), the determination of the primary or secondary nature of ES is important. Indeed, the association of ES with other diseases such as haematological malignancies, systemic lupus erythematosus, infections, or primary immune deficiencies can interfere with its management or alter its prognosis. Due to the rarity of the disease, the treatment of ES is mostly extrapolated from what is recommended for isolated AIC and mostly relies on corticosteroids, rituximab, splenectomy, and supportive therapies. The place for thrombopoietin receptor agonists, erythropoietin, immunosuppressants, haematopoietic cell transplantation, and thromboprophylaxis is also discussed in this review. Despite continuous progress in the management of AIC and a gradual increase in ES survival, the mortality due to ES remains higher than the ones of isolated AIC, supporting the need for an improvement in ES management.
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PMID:Evans' Syndrome: From Diagnosis to Treatment. 3326 Sep 79