Response to imatinib mesylate in patients with hypereosinophilic syndrome

Arefi, Maryam; Garcı́a, Juan Luis; Briz, Montserrat; Arriba, Felipe de; Rodríguez, Juan Nicolás; Martín–Núñez, Guillermo; Martı́nez, Javier; López, Javier; Suárez, J. García; Moreno, Manuel Sánchez; Merino, M.A.; Gutiérrez, Norma C.; Hernández‐Rivas, Jesús María

doi:10.1007/s12185-012-1141-7

Cited by 16 publications

(12 citation statements)

References 26 publications

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“…Several IGF1R inhibitors are currently under development for the treatment of various types of cancer (20). Our data indicate that the IGF1R inhibitors could potentially also be used to treat patients with eosinophilia, such as the hypereosinophilic syndrome (21). Furthermore, we have identified miR-223 as a regulator of eosinophil IGF1R levels.…”

Section: Discussionmentioning

confidence: 84%

miR-223 Deficiency Increases Eosinophil Progenitor Proliferation

Lim

Besse

et al. 2013

The Journal of Immunology

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Recently, microRNAs (miRNAs) have been shown to be involved in hematopoietic cell development but their role in eosinophilopoeisis has not yet been described. Here we show that miR-223 is up-regulated during eosinophil differentiation in an ex vivo bone marrow derived eosinophil culture system. Targeted ablation of miR-223 leads to an increased proliferation of eosinophil progenitors. We found up-regulation of a miR-223 target gene – IGF1R in the eosinophil progenitor cultures derived from miR-223-/- mice compared to miR-223+/+ littermate controls. The increased proliferation of miR-223-/- eosinophil progenitors was reversed by treatment with the IGF1R inhibitor (picropodophyllin). Whole genome microarray analysis of differentially regulated genes between miR-223+/+ and miR-223-/- eosinophil progenitor cultures identified a specific enrichment in genes that regulate hematologic cell development. Indeed, miR-223-/- eosinophil progenitors had a delay in differentiation. Our results demonstrate that miRNAs regulate the development of eosinophils by influencing eosinophil progenitor growth and differentiation and identify a contributory role for miR-223 in this process.

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Section: Discussionmentioning

confidence: 84%

miR-223 Deficiency Increases Eosinophil Progenitor Proliferation

Lim

Besse

et al. 2013

The Journal of Immunology

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“…Imatinib activity at the molecular level in HES remains unclear [6]. Low dose Imatinib (100mg/day) has resulted in haematological and molecular remission in most of the patients [7].…”

Section: Discussionmentioning

confidence: 99%

A Case of Erythroderma Secondary to Hypereosinophilia

Abdulsalam

Ghanta

Pandurangan

et al. 2016

JCDR

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A 67-year-old female was admitted to our emergency in altered sensorium with generalized erythroderma and patchy hair loss. She underwent splenectomy for lymphangioma [Table/ Fig-1] six months before. Clinical examination showed erythroderma, sacral edema, mucosal dark pigmented lesions, patchy hair loss and madarosis. Basic laboratory investigations showed anaemia (Haemoglobin-7.3 gm/dl), leucocytosis (White blood cell count-19,000/c.mm) with hypereosinophilia (Absolute eosinophil count : 11,768/c.mm) and thrombocytosis (5,08,000/c.mm).She had severe hypoalbuminemia (albumin -1.9 gm/dl) probably secondary to loss of protein through skin. Anti-nuclear antibody (ANA), anti-double stranded DNA (anti-Ds DNA) and antineutrophil cytoplasmic antibody (ANCA) were negative. In the absence of any significant history of atopy, allergic disorders, or parasites to explain her high eosinophil counts she was submitted to a work up for primary hypereosinophilia and any associated end organ damage. In view of high Vitamin B12 levels (16,680ng/L) and hypereosinophilia, there was a strong suspicion of myeloproliferative disorders. Molecular genetic work up showed absence of Fip1-like-1 fused with platelet derived growth factor receptor alpha (FIP1L1-PDGFRα) and BCR-ABL mutation. Bone marrow biopsy showed scanty marrow with eosinophilia [Table/ Fig-2].T-cell receptor rearrangement studies were done and primary cutaneous T cell lymphoma was ruled out. A skin biopsy showed subcorneal eosinophilic collection with spongiotic dermatitis [ Hypereosinophilic syndrome (HES) is a myeloproliferative disorder characterised by marked peripheral eosinophilia and end organ damage attributable to eosinophilia without secondary cause. Early recognition and treatment are essential to prevent morbidity and mortality. Cytoreduction with Steroids, Hydroxyurea and Imatinib are the main stay of treatment. Molecular studies like Fip1-like-1 fused with platelet derived growth factor receptor alpha (FIP1L1-PDGFRα) etc., are recommended in view of therapeutic implication. In this paper we report a rare case of HES developing in a lady 6 months after surgical removal of lymphangioma of spleen, which in itself is rare.

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“…These conditions cause persistent hepatocellular damage and regeneration; consequently, there are associated with the subsequent of hepatocellular carcinoma(HCC). Thus, HGF-HGF receptor signaling might play an important role in carcinogenesis [163,167]. PRS-110 (starting at 0.8 mg/kg and going up to 30 mg/kg) specifically binds to Met receptor with high affinity and blocks HGF interaction on ligand-dependent (U87-MG) and ligand-independent (Caki-1) xenograft model [162].…”

Section: Targeting Oncogenic Growth Factor Receptorsmentioning

confidence: 99%

Downregulating oncogenic receptor: From bench to clinic

Zhu¹,

Saboor-Yaraghi²,

Yarden³

et al. 2016

Hematol Med Oncol

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as a result of his experiments in which steroid PML-RARa fusion receptor gene rearrangement within it(15;17) translocation in acute promyelocytic leukemia (APL), FGFR-1) receptor induced tumours of the breast glands in two aplastic anemia during the course of testosterone treatment (hormonal tumorigenesis). In the past 2-3 decades, there are at least 30 receptor genes involving in various of oncogenic process. These normal physiologic receptors linked to gene amplification, rearrangement, deletion and activating mutations, which converted receptor to oncogenic (also oncogenic receptor) in development, progressive and pathogenesis of benign and malignant diseases. Receptors included nuclear receptor family members (oncogenic estrogen/estrogen receptor alpha signaling, oncogenic androgen receptor, oncogenic receptor pml/RARa, and GRβ); Oncogenic growth factor receptors (EGF/oncogenic receptor EGFR, Neu oncogenic receptor, insulin receptor substrate 4 IRS4/insulin receptor/c-ros protooncogenic receptor, insulin and IGF-1 and -II/oncogenic IGF-1R, oncogenic PDGFAR, oncogenic TEL/PDGFRB, HGF/HGFR、met oncogenic receptor); Cytokine receptor rc family members (IL-2-BCM fusion,IL-3/oncogenic IL-3Ra,IL-7/oncogenic IL-7R and IL-21R-BCL6 fusion); Cytokine receptors including the βc family (G-CSF/oncogenic CSF3R,oncogenic EPOR), and oncogenic autocrine growth hormone/nuclear GHR and other VEGFR2. Upon ligand binding or external antigen stimuli, mutated growth factor receptors and mutant cytokine receptors including type I cytokine receptor may be activated via ligand binding receptor complex, receptor dimerizes especially receptor homodimerization, and induces transphosphorylation of tyrosine residues in the cytoplasmic domains which serves as docking sites for several adaptor molecular harboring SH2 domain or phosphotyrosine binding domain. These adaptor molecules recruit and activate downstream signaling molecules such as Ras/MAPK, phospholipase C-r,JAK-STAT molecules, NF-KB pathways through tyrosine-or serine/threnonine-phosphorylation. Among them, Ras /MAPK/ERK, PI3-K/akt and STAT pathways act as the major oncogenic signaling pathway. Overall, these receptors coupled with their ligands are key importance in human subtle balance in physically regulating multiple cellular processes, for example, in cellular proliferation and differentiation. Oncogenic receptors mutational activation and/or aberrant gene rearrangement are promiscuously interference with normal cell survival, anti-apoptosis and proliferation, and malignant initiation and progression. Others, in a special APL case, oncogenic pml/RARa fusion behave as a potent (constitutive) transcriptional repressor of RAR and retinoic acid signaling, inducing a differentiation blockage at promyelocytic stage which can be overcome with therapeutic doses of 9-cis retinoic acid or ATRA ligand (see in detail model,

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Response to imatinib mesylate in patients with hypereosinophilic syndrome

Cited by 16 publications

References 26 publications

miR-223 Deficiency Increases Eosinophil Progenitor Proliferation

miR-223 Deficiency Increases Eosinophil Progenitor Proliferation

A Case of Erythroderma Secondary to Hypereosinophilia

Downregulating oncogenic receptor: From bench to clinic

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