Eosinophilic states that may occur in association with Loeffler endocarditis include hypereosinophilic syndrome, eosinophilic leukemia, carcinoma, lymphoma, drug reactions or parasites, as reported in multiple case series. (medscape.com)
Idiopathic hypereosinophilic syndrome (HES) is a rare disorder characterized by peripheral eosinophilia exceeding 1500/mm 3 , a chronic course, absence of secondary causes, and signs and symptoms of eosinophil-mediated tissue injury. (wjgnet.com)
Adult patients with hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL) who have FIP1L1-PDGFRα fusion kinase (mutational analysis or FISH demonstration of CHIC2 allele deletion) and for patients with HES and/or CEL who are FIP1L1-PDGFRα fusion kinase negative or unknown. (hikma.com)
Elling C, Erben P, Walz C, Frickenhaus M, Schemionek M, Stehling M. Novel imatinib-sensitive PDGFRA-activating point mutations in hypereosinophilic syndrome induce growth factor independence and leukemia-like disease. (medscape.com)
Specifically, it is used for chronic myelogenous leukemia treatment (CML) and acute lymphocytic leukemia (ALL) that are Philadelphia chromosome-positive (Ph+), certain types of gastrointestinal stromal tumors (GIST), hypereosinophilic syndrome (HES), chronic eosinophilic leukemia (CEL), systemic mastocytosis, and myelodysplastic syndrome. (theindianpharma.com)
The FIP1-like-1-platelet-derived growth factor receptor alpha (FIP1L1-PDGFRα) fusion oncogene is the driver factor in a subset of patients with hypereosinophilic syndrome (HES)/chronic eosinophilic leukemia (CEL). (oncotarget.com)
Besides genetics, ICC for the first time has introduced bone marrow morphologic criteria in distinguishing idiopathic hypereosinophilia/hypereosinophilic syndrome from chronic eosinophilic leukemia, not otherwise specified. (bvsalud.org)
Myeloid9
Differential diagnoses include drug allergies and parasitic infections, solid and hematological malignancies (i.e. chronic myeloid leukemia), eosinophilic granulomatosis with polyangiitis and human T cell lymphotropic virus infection (see these terms). (orpha.net)
Newly diagnosed adult and pediatric patients with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase. (hikma.com)
Patients with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in blast crisis (BC), accelerated phase (AP), or in the chronic phase (CP) after failure of interferon-alpha therapy. (hikma.com)
Gleevec (imatinib) is FDA approved for c-KIT positive GIST and dermatofibrosarcoma protuberans, Philadelphia chromosome positive chronic myeloid leukemia, and FIP1L1-PDGFRA positive chronic eosinophilic leukemia (FDA.gov). (jax.org)
Imatinib basically inhibits the proliferation and it also induces apoptosis in bcr-abl positive cell lines as well as maiden or fresh leukemic cells from the Philadelphia chromosome positive chronic myeloid leukemia. (theindianpharma.com)
In the Vivo, imatinib inhibits the growth of tumor of bcr-abl transfected murine myeloid cells as well as bcr-abl positive leukemia lines derived from the CML patients in the blast crisis. (theindianpharma.com)
Гострий мієлоїдний лейкоз (ГМЛ) In acute myeloid leukemia (AML), malignant transformation and uncontrolled proliferation of an abnormally differentiated, long-lived myeloid progenitor cell results in high circulating numbers. (msdmanuals.com)
Dasatinib (Sprycel): Indicated for the treatment of adult patients with chronic myeloid leukemia in chronic, accelerated, or myeloid or lymphoid blast phase who are resistant or intolerant to prior therapy including imatinib. (medscape.com)
Veenat 400mg(Imatinib 400mg) is also knowns as tyrosine kinase inhibitor that interferes with the BCR-ABL tyrosine kinase produced by the Philadelphia chromosome abnormality in chronic myeloid (blood cancer) leukaemia(CML). (myapplepharma.com)
Systemic mastocytosis1
Based on new data and increased understanding of disease molecular genetics, the international consensus classification (ICC) has made several changes in the diagnosis and classification of eosinophilic disorders and systemic mastocytosis. (bvsalud.org)
Eosinophilia2
Additionally, idiopathic eosinophilic endomyocarditis, in the absence of peripheral eosinophilia, has been reported by Priglinger et al. (medscape.com)
Eosinophilia can be found in a variety of benign and malignant conditions, and a persistent eosinophilic count of more than 1500/mm necessitates additional investigation. (iasp-pain.org)
PDGFRA14
Although imatinib is clearly the treatment of choice for FIP1L1/PDGFRA-positive chronic eosinophilic leukemia (CEL), little is known about optimal dosing, duration of treatment, and the possibility of cure in this disorder. (elsevierpure.com)
To address these questions, 5 patients with FIP1L1/PDGFRA positive CEL with documented clinical, hematologic, and molecular remission on imatinib (400 mg daily) and without evidence of cardiac involvement were enrolled in a dose de-escalation trial. (elsevierpure.com)
These data are consistent with suppression rather than elimination of the clonal population in FIP1L1/PDGFRA-positive CEL and suggest that molecular monitoring may be the most useful method in determining optimal dosing without the risk of disease exacerbation. (elsevierpure.com)
The FIP1L1-PDGFRA mutation was the first description of a gain of function mutation resulting from an interstitial deletion instead of a chromosomal translocation. (wikipedia.org)
The FIP1L1-PDGFRA fusion gene consists of the 5'-end of FIP1L1 united to the 3'-end of PGDFRA at variable breakpoints in both genes extending over a 40 kilobase region in FIP1L1 and a small region of exon 12 in PDGFRA. (wikipedia.org)
The fusion gene may produce a protein consisting of the first 233 amino acids of FIP1L1 joined to the last 523 amino acids of PDGFRA or fused proteins consisting of other FIP1L1 and PDGFRA amino acid lengths. (wikipedia.org)
The known FIP1L1-PDGFRA fusion proteins exhibit similar if not identical pathological activities. (wikipedia.org)
FIP1L1-PDGFRA fusion genes have been detected in the eosinophils, neutrophils, mast cells, monocytes, T lymphocytes, and B lymphocytes involved in hematological malignancies. (wikipedia.org)
FIP1L1-PDGFRA fusion proteins retain PDGFRA-related Tyrosine kinase activity but, unlike PDGFRA, their tyrosine kinase is constitutive, i.e. continuously active: the fusion proteins lack the intact protein's 3'-end that includes its juxtamembrane domain which normally blocks tyrosine kinase activity unless PDGFRA is bound to its activating ligand, platelet-derived growth factor. (wikipedia.org)
FIP1L1-PDGFRA fusion proteins are also resistant to PDGFRA's normal pathway of degradation, i.e. (wikipedia.org)
One of the best-characterized forms of HES is the one associated with FIP1L1-PDGFRA gene rearrangement, which was recently demonstrated as responsive to treatment with the small molecule kinase inhibitor drug, imatinib mesylate. (wjgnet.com)
Patients with FIP1L1-PDGFRA-positive chronic eosinophilic leukemia might present as asymptomatic or in a catastrophic state with multi-organ involvement. (iasp-pain.org)
We present the case of a young male patient who was diagnosed with FIP1L1-PDGFRA chronic eosinophilic leukemia after a long history of recurrent cutaneous symptoms with no systemic signs. (iasp-pain.org)
Patients with the FIP1L1/PDGFRA -associated fusion gene are more often males and may be responsive to low-dose imatinib (a tyrosine kinase inhibitor). (msdmanuals.com)
Imatinib Mesylate1
In a randomized trial in patients with newly diagnosed Ph+ CML in chronic phase comparing imatinib mesylate and nilotinib, severe (Grade 3 or 4) fluid retention occurred in 2.5% of patients receiving imatinib mesylate and in 3.9% of patients receiving nilotinib 300 mg twice daily. (hikma.com)
Acute5
[ 3 ] Pathologic specimens in Loeffler endocarditis show eosinophilic myocarditis, a tendency toward endomyocardial fibrosis and clinical manifestations of thromboembolism, and acute heart failure. (medscape.com)
[ 10 ] Myocardial involvement is less well known and has been considered a manifestation of an acute necrotic stage of eosinophilic endomyocardial disease, as reported by Olsen and colleagues. (medscape.com)
Adult patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). (hikma.com)
Myeloproliferative diseases are a heterogeneous group of disorders characterized by cellular proliferation of one or more hematologic cell lines in the peripheral blood, distinct from acute leukemia. (medscape.com)
They are also at risk of developing secondary acute leukemia from their underlying disorder, as well as from their treatment. (medscape.com)
Patients3
Pediatric patients with Ph+ CML in chronic phase who are newly diagnosed or whose disease has recurred after stem cell transplant or who are resistant to interferon-alpha therapy. (theindianpharma.com)
Most FIP1L1-PDGFRα-positive patients respond well to the tyrosine kinase inhibitor (TKI) imatinib. (oncotarget.com)
Hematopoietic stem cell transplantation can be considered in young patients with chronic myelogenous leukemia in chronic phase if a human leukocyte antigen (HLA)-matched donor is available. (medscape.com)
Myocarditis2
[ 4 ] Herzog et al and Tonnesen et al have proposed that the reason for this situation may be the rapidly fatal evolution of most cases of eosinophilic arteritis and myocarditis. (medscape.com)
[ 11 ] More recently, cases of isolated eosinophilic myocarditis have been reported without signs of endomyocardial involvement, with or without vasculitis. (medscape.com)
Myelogenous leukemia1
Bone marrow fibrosis is also detected in the spent phase of chronic myelogenous leukemia and polycythemia vera. (medscape.com)
Infiltration2
Although eosinophilic endocardial disease has been well described, myocardial and vascular damage due to eosinophilic infiltration and degranulation is rarely diagnosed during life, as reported by Oakley et al and others. (medscape.com)
1.5 109/L) and /or eosinophilic infiltration of tissue(s) responsible for target-organ damage. (orpha.net)
Mutation1
Resistance to imatinib in HES/CEL has been described mainly due to the T674I mutation in FIP1L1-PDGFRα, which is homologous to the imatinib-resistant T315I mutation in BCR-ABL. (oncotarget.com)
Clonal1
A medically important aspect of the FIP1L1 gene is its fusion with other genes to form fusion genes which cause clonal hypereosinophilia and leukemic diseases in humans. (wikipedia.org)
Subunit1
FIP1L1 is a subunit of the cleavage and polyadenylation specificity factor subunit 1 (CPSF1) complex that polyadenylates the 3' end of precursor mRNAs (pre-mRNA) (see CPSF). (wikipedia.org)
Proteins3
[ 13 ] Spry et al reported eosinophilic degranulation of basic proteins causing myocardial damage in tissue cultures in vitro. (medscape.com)
[ 14 ] Gliech et al reported a dose-dependent cytotoxic effect of the eosinophilic granular proteins, inhibiting multiple enzyme systems. (medscape.com)
The cationic eosinophilic proteins bind to the anionic endothelial protein, thrombomodulin. (medscape.com)
Fusions1
FIP1L1 gene fusions between it and either the platelet-derived growth factor receptor, alpha (PGDFRA) or Retinoic acid receptor alpha (RARA) genes are causes of certain human diseases associated with pathologically increased levels of blood eosinophils and/or Leukemias. (wikipedia.org)
Fusion2
In humans, an interstitial chromosomal deletion of about 800 kilobases at 4q12 deletes the CHIC2 gene (i.e.cysteine rich hydrophobic domain 2 gene) to create an in-frame fusion of the FIP1L1 gene with the platelet-derived growth factor receptor alpha gene (PGDFRA) gene. (wikipedia.org)
RARA, (17q12) at various points yields a (15;17)(q22;q21) fusion gene, FIP1L1-RARA that also has been implicated in the development of human leukemic diseases in three case reports. (wikipedia.org)
Chromosome1
The human FIP1L1 gene is located on chromosome 4 at position q12 (4q12), contains 19 exons, and codes for a complete protein consisting of 594 amino acids. (wikipedia.org)
Positive1
Pruritus as a Presenting Symptom of -Positive Chronic Eosinophilic Leukemia. (iasp-pain.org)
Distinct1
However, alternative splicing of its Precursor mRNA results in multiple transcript variants encoding distinct FIP1L1 protein isoforms. (wikipedia.org)
Assays1
FIP1L1/PDGFR point mutations often camouflage assays, but do not necessarily affect imatinib effectiveness. (medscape.com)
Activity1
In this study, we evaluated the antitumor activity of S116836 in FIP1L1-PDGFRα-expressing cells. (oncotarget.com)
Cells2
S116836 effectively inhibited the growth of the WT and T674I FIP1L1-PDGFRα-expressing neoplastic cells in vitro and in nude mouse xenografts. (oncotarget.com)
In conclusion, S116836 is active against WT and T674I FIP1L1-PDGFRα-expressing cells, and may be a prospective agent for the treatment of HES/CEL. (oncotarget.com)
Alpha1
A Chromosomal translocation of FIP1L1 (4q12) with the Retinoic acid receptor alpha gene, i.e. (wikipedia.org)
Factor2
also termed Pre-mRNA 3'-end-processing factor FIP1) is a protein that in humans is encoded by the FIP1L1 gene (also known as Rhe, FIP1, and hFip1). (wikipedia.org)
This poly-adenylyl action increases pre-mRNA's maturation and movement from the nucleus to cytoplasm while also increasing the stability of the mRNA formed from pre-mRNA: FIP1L1 is a Pre-mRNA 3'-end-processing factor. (wikipedia.org)
Responsible1
The FIP1 motif of 40 amino acids on FIP1L1 is responsible for its binding to CPSF1. (wikipedia.org)