• chronic eosinophilic leukaemia
• diagnosis
• eosinophil disorders
• myeloproliferative neoplasm
• treatment

• Humans
• Hypereosinophilic Syndrome/genetics
• Hypereosinophilic Syndrome/therapy
• Hypereosinophilic Syndrome/diagnosis
• Prognosis
• Genomics/methods
• Disease Management
• Leukemia

• FIP1L1-PDGFRA
• chronic eosinophilic leukemia
• eosinophilia
• hypereosinophilic syndrome

• NETosis
• dermal microvascular unit
• leukocytoclastic
• vasculitis histopathology
• vasculitis pathogenesis

• Humans
• Vasculitis/pathology
• Vasculitis/etiology
• Skin/pathology
• Skin/blood supply
• Neutrophils/pathology
• Lymphocytes/pathology
• Lymphocytes/immunology
• Skin Diseases, Vascular/pathology
• Skin Diseases, Vascular/immunology
• Skin Diseases, Vascular/etiology
• Skin Diseases, Vascular/diagnosis

• Humans
• Hodgkin Disease/complications
• Hodgkin Disease/diagnosis
• Hodgkin Disease/pathology
• Hypereosinophilic Syndrome/complications
• Hypereosinophilic Syndrome/diagnosis

• acute myocarditis
• cardiac magnetic resonance
• chronic inflammatory cardiomyopathy
• endomyocardial biopsy
• heart failure

• FIP1L1–PDGFRA fusion gene
• Loeffler endocarditis
• cardiac imaging
• heart failure
• hypereosinophilic syndrome

• 615/13/17.01.2019 George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Romania

• IgG4-related disease
• eosinophilia
• hypereosinophilic syndrome

• leukemia
• molecular diagnosis
• pediatric cancer

• Corticosteroids
• Eosinophil
• Hypereosinophilic syndrome
• IgG4

• CRS
• Dupilumab
• Hypereosinophilia
• Nasal polyps

• Heart
• Humans
• Hypereosinophilic Syndrome/diagnosis
• Hypereosinophilic Syndrome/drug therapy
• Hypersensitivity
• Myocarditis/diagnosis
• Myocarditis/etiology
• Myocardium

• EGPA
• IgE
• eosinophils
• fungal
• hypereosinophilic syndrome
• parasites

• chronic eosinophilic leukemia
• hypereosinophilia

Eosinophil granulocytes (eosinophils) belong to the family of white blood cells that play important roles in the development of asthma and various types of allergy. Eosinophils are cells with a diameter of 12–17 µm and they originate from myeloid precursors. They were discovered by Paul Ehrlich in 1879 in the process of staining fixed blood smears with aniline dyes. Apoptosis (programmed cell death) is the process by which cells lose their functionality. Therefore, it is very important to study the apoptosis of eosinophils and their survival factors to understand how to develop new drugs based on the modulation of eosinophil apoptosis for the treatment of asthma and allergic diseases.

In the past 10 years, the number of people in the Czech Republic with allergies has doubled to over three million. Allergic pollen catarrh, constitutional dermatitis and asthma are the allergic disorders most often diagnosed. Genuine food allergies today affect 6–8% of nursing infants, 3–5% of small children, and 2–4% of adults. These disorders are connected with eosinophil granulocytes and their apoptosis. Eosinophil granulocytes are postmitotic leukocytes containing a number of histotoxic substances that contribute to the initiation and continuation of allergic inflammatory reactions. Eosinophilia results from the disruption of the standard half-life of eosinophils by the expression of mechanisms that block the apoptosis of eosinophils, leading to the development of chronic inflammation. Glucocorticoids are used as a strong acting anti-inflammatory medicine in the treatment of hypereosinophilia. The removal of eosinophils by the mechanism of apoptosis is the effect of this process. This work sums up the contemporary knowledge concerning the apoptosis of eosinophils, its role in the aforementioned disorders, and the indications for the use of glucocorticoids in their related therapies.

• allergy
• apoptosis
• eosinophil granulocyte
• inflammation

Hypereosinophilic syndromes (HESs) are a group of disorders characterized by pathological proliferation of eosinophils. Diagnostic criteria include eosinophil count of 1,500/mm³ or higher, presence of organ involvement and exclusion of other causes of eosinophilia for at least 6 months. A 69-year-old male patient was referred to the pandemic clinic with a preliminary diagnosis of coronavirus disease 2019 (COVID-19) with fever and dyspnea. Computed tomography (CT) was compatible with COVID-19, nasopharyngeal swab polymerase chain reaction (PCR) was negative for two times. He had 20,000/mm³ eosinophilia and retrospective examinations showed that he have had eosinophilia for more than 1 year. Platelet-derived growth factor receptor alpha (PDGFRα) resulted positively. After starting parenteral methylprednisolone with a dose of 1 mg/kg, he was discharged with oral maintenance therapy. In outpatient follow-up, it was observed that eosinophilic pneumonia completely regressed. HES may occur with multiple system and organ involvement and findings. In the differential diagnosis of patients presenting with heart failure, pulmonary involvement and eosinophilia, HES must definitely be considered.

• COVID-19
• Eosinophilia
• Hypereosinophilic syndrome
• Pulmonary involvement

Hypereosinophilic syndrome (HES) is an uncommon syndrome characterized by peripheral blood eosinophils count of more than 1,500/mm³ with associated tissue damage. It can be either primary or secondary, for example, due to parasitic infections or inflammation.

We present a case of a 49-year-old Asian female with recurrent hospital admissions for cholecystitis, gastritis, urinary cystitis, and pancreatitis. Her peripheral blood count showed excessive eosinophils 15,600-19,000/mm³ on different occasions. Pathology of her gallbladder and her gastric biopsies showed eosinophilic infiltration. Her bone marrow biopsy showed a normocellular marrow with active trilineage hematopoiesis, eosinophilia, mild megakaryocytic hyperplasia with a few atypical forms, and mild T-cell lymphocytosis. Flow cytometry showed no evidence of acute leukemia, or T-cell or B-cell lymphoproliferative disorder. On fluorescent in-situ hybridization (FISH), myeloproliferative neoplasms (MPN) testing was negative for platelet-derived growth factor receptor-alpha (PDGFRA), platelet-derived growth factor receptor-beta (PDGFRB), and fibroblast growth factor receptor-1 (FGFR1) rearrangement. Despite not having the FIP1L1‐PDGFRA (factor interacting with PAPOLA and CPSF1-platelet-derived growth factor receptor, alpha polypeptide) gene fusion, our patient responded to the treatment with a significant decrease in her absolute eosinophils count and resolution of her symptoms.

• eosinophilic cholecystitis
• eosinophilic cystitis
• eosinophilic pancreatitis
• hypereosinophilic syndrome
• imatinib
• myeloproliferative neoplasm

Thrombosis events usually occur after prolonged bedrest, pregnancy, hormonal therapy, recent surgery and in the presence of inherited or acquired thrombophilia. However, several other diseases are often associated with thrombosis although their frequency is not easily estimated. Eosinophilia is one of these conditions. From a clinical viewpoint it is very difficult to understand which conditions might lead to a thrombotic event because the underlying pathophysiological mechanisms are different. Here, we report a case of idiopathic hypereosinophilia associated to venous thromboembolism without any other associated prothrombotic condition.

• allergy
• deep vein thrombosis
• hypereosinophilia
• venous thromboembolism

• cyclosporine
• hypereosinophilic syndrome
• interferon-α
• lymphocyte variant hypereosinophilia
• malignant lymphoma

• Basket trials
• Genomic analysis
• Kinase inhibitors
• Rare cancers
• Umbrella trials

• Genomics
• Humans
• Molecular Targeted Therapy
• Neoplasms/diagnosis
• Neoplasms/genetics
• Precision Medicine
• Prognosis

• dermatology
• general practice/family
• haematology (incl blood transfusion)
• medical management
• skin

• CEL-NOS
• Decitabine
• Hypereosinophilia
• NPM1 mutation
• Secondary AML

• Aged
• Antiparasitic Agents/administration & dosage
• Eosinophilia/complications
• Eosinophilia/diagnosis
• Eosinophilia/drug therapy
• Feces/parasitology
• Female
• Humans
• Intestinal Diseases, Parasitic/complications
• Intestinal Diseases, Parasitic/diagnosis
• Intestinal Diseases, Parasitic/drug therapy
• Ivermectin/administration & dosage

• Adolescent
• Antineoplastic Agents/therapeutic use
• Biopsy
• Bone Marrow/pathology
• Chromosomal Proteins, Non-Histone/genetics
• Chromosome Banding
• Dasatinib/therapeutic use
• Humans
• Immunohistochemistry
• Leukemia, Myeloid, Acute/diagnosis
• Leukemia, Myeloid, Acute/drug therapy
• Leukemia, Myeloid, Acute/genetics
• Male
• Nuclear Pore Complex Proteins/genetics
• Nuclear Proteins/genetics
• Oncogene Proteins/genetics
• Oncogene Proteins, Fusion/genetics
• Poly-ADP-Ribose Binding Proteins/genetics
• Protein Kinase Inhibitors/therapeutic use
• Receptor, Platelet-Derived Growth Factor beta/genetics
• Receptors, Cytoplasmic and Nuclear/genetics
• Repressor Proteins/genetics
• Translocation, Genetic
• Treatment Outcome

Idiopathic hypereosinophilia (IHE)/idiopathic hypereosinophilic syndrome (IHES) has been defined by a persistent elevation of the blood eosinophil count exceeding 1.5×10³/μL, without evidence of reactive or clonal causes. While T-cell clonality assessment has been recommended for unexplained hypereosinophilia, this approach is not often applied to routine practice in the clinic. We hypothesized that the clonality would exist in a subset of IHE/IHES patients. We aimed to investigate the candidate mutations and T-cell clonality in IHE/IHES and to explore the role of mutations in eosinophil proliferation. We performed targeted capture sequencing for 88 genes using next-generation sequencing, T-cell receptor (TCR) gene rearrangement assays, and pathway network analysis in relation to eosinophil proliferation. By targeted sequencing, 140 variants in 59 genes were identified. Sixteen out of 30 patients (53.3%) harbored at least one candidate mutation. The most frequently affected genes were NOTCH1 (26.7%), SCRIB and STAG2 (16.7%), and SH2B3 (13.3%). Network analysis revealed that our 21 candidate genes (BIRC3, BRD4, CSF3R, DNMT3A, EGR2, EZH2, FAT4, FLT3, GATA2, IKZF, JAK2, MAPK1, MPL, NF1, NOTCH1, PTEN, RB1, RUNX1, TET2, TP53 and WT1) are functionally linked to the eosinophilopoietic pathway. Among the 21 candidate genes, five genes (MAPK1, RUNX1, GATA2, NOTCH1 and TP53) with the highest number of linkages were considered major genes. A TCR assay revealed that four patients (13.3%) had a clonal TCR rearrangement. NOTCH1 was the most frequently mutated gene and was shown to be a common node for eosinophilopoiesis in our network analysis, while the possibility of hidden T cell malignancy was indwelling in the presence of NOTCH1 mutation, though not revealed by aberrant T cell study. Collectively, these results provide new evidence that mutations affecting eosinophilopoiesis underlie a subset of IHE/IHES, and the candidate genes are inferred to act their potential roles in the eosinophilopoietic pathway.

• Central nervous system
• hypereosinophilic syndrome
• magnetic resonance imaging (MRI)
• small-vessel disease

• Eosinophilic funiculitis
• Groin tumor
• Irreducible inguinal hernia

• Pneumonia
• eosinophile
• lymphoma

Idiopathic hypereosinophilic syndrome (HES) is a rare disorder characterized by peripheral eosinophilia exceeding 1500/mm³, a chronic course, absence of secondary causes, and signs and symptoms of eosinophil-mediated tissue injury. 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. Here, we describe the case of a 51-year-old male, whose symptoms satisfied the clinical criteria for HES with cutaneous and cardiac involvement and who also presented with vasculitic brain lesions and retroperitoneal bleeding. Molecular testing, including fluorescence in situ hybridization, of bone marrow and peripheral blood showed no evidence of PDGFR rearrangements. The patient was initially treated with high-dose steroid therapy and then with hydroxyurea, but proved unresponsive to both. Upon subsequent initiation of imatinib mesilate, the patient showed a dramatic improvement in eosinophil count and progressed rapidly through clinical recovery. Long-term follow-up confirmed the efficacy of treatment with low-dose imatinib and with no need of supplemental steroid treatment, notwithstanding the absence of PDGFR rearrangement.

• Idiopathic hypereosinophilic syndrome
• Eosinophilia
• Cerebral vasculitis
• PDGFR molecular rearrangement
• Imatinib mesilate

• Abdominal Pain/etiology
• Aged, 80 and over
• Diagnosis, Differential
• Exanthema/etiology
• Fatal Outcome
• Fever/etiology
• Humans
• Lymphoma, T-Cell/complications
• Lymphoma, T-Cell/diagnosis
• Lymphoma, T-Cell/pathology
• Male

• Adult
• Azathioprine/therapeutic use
• Endomyocardial Fibrosis/drug therapy
• Endomyocardial Fibrosis/etiology
• Female
• Heart Failure/drug therapy
• Heart Failure/etiology
• Humans
• Hypereosinophilic Syndrome/complications
• Immunosuppressive Agents/therapeutic use
• Prednisone/therapeutic use
• Pregnancy

Activating mutations of KIT receptor tyrosine kinase have been reported in different neoplasms. The M541L KIT substitution (KIT^M541L) has been described to be associated with pediatric mastocytosis, to enhance growth rate of the affected cells and to confer higher sensitivity to imatinib therapy. We investigated the presence of KIT^M541L in five males with chronic eosinophilic leukemia, not otherwise specified (CEL, NOS), all negative for Platelet-derived growth factor-alpha (PDGFR) or PDGFRbeta abnormalities, which responded to imatinib therapy. To assess whether the mutation was constitutive or somatic in nature, we evaluated its presence analyzing either the neoplastic or normal cell population (epidermal cells or CD3-positive T lymphocytes). KIT^M541L substitution was found in 4 out of 5 patients and in all it was somatic in nature. All patients were treated with low dose imatinib (100 mg daily orally), achieving complete and persistent clinical and hematological remission (median follow-up 74 months). One patient relapsed after 50 months. Our study strongly suggests to search for the KIT^M541L in patients with CEL, NOS, negative for PDGFRalpha and PDGFRbeta abnormalities, to identify a subgroup of cases who may benefit from low dose imatinib therapy.

• Adult
• Antineoplastic Agents/administration & dosage
• Benzamides/administration & dosage
• Eosinophilia/drug therapy
• Eosinophilia/metabolism
• Follow-Up Studies
• Humans
• Imatinib Mesylate
• Leukemia, Myeloid/diagnosis
• Leukemia, Myeloid/drug therapy
• Leukemia, Myeloid/metabolism
• Male
• Oncogene Proteins, Fusion/drug effects
• Oncogene Proteins, Fusion/isolation & purification
• Oncogene Proteins, Fusion/metabolism
• Piperazines/administration & dosage
• Pyrimidines/administration & dosage
• Receptor, Platelet-Derived Growth Factor alpha/drug effects
• Receptor, Platelet-Derived Growth Factor alpha/isolation & purification
• Receptor, Platelet-Derived Growth Factor alpha/metabolism
• Treatment Outcome
• mRNA Cleavage and Polyadenylation Factors/drug effects
• mRNA Cleavage and Polyadenylation Factors/isolation & purification
• mRNA Cleavage and Polyadenylation Factors/metabolism

• Adult
• Angiography
• Echocardiography
• Electrocardiography
• Heart Diseases/diagnosis
• Heart Diseases/etiology
• Heart Ventricles
• Humans
• Hypereosinophilic Syndrome/complications
• Male
• Middle Aged
• Multidetector Computed Tomography
• Thrombosis/diagnosis
• Thrombosis/etiology
• Tomography, Emission-Computed

Deregulated protein tyrosine kinase activity is central to the pathogenesis of human cancers. Targeted therapy in the form of selective tyrosine kinase inhibitors (TKIs) has transformed the approach to management of various cancers and represents a therapeutic breakthrough. Imatinib was one of the first cancer therapies to show the potential for such targeted action. Imatinib, an oral targeted therapy, inhibits tyrosine kinases specifically BCR-ABL, c-KIT, and PDGFRA. Apart from its remarkable success in CML and GIST, Imatinib benefits various other tumors caused by Imatinib-specific abnormalities of PDGFR and c-KIT. Imatinib has also been proven to be effective in steroid-refractory chronic graft-versus-host disease because of its anti-PDGFR action. This paper is a comprehensive review of the role of Imatinib in oncology.