Objective: Analysis of the molecular characteristics of eosinophilia. Methods: Targeting sequence to 24 patients with chronic eosinophilic leukemia (CEL) with rearrangement of PDGFRA, PDGFRB, or FGFR1 and 62 patients with hyper-eosinophilic syndrome (HES). Mutation annotation and analysis of amino acid mutation using authoritative databases to speculate on possible pathogenic mutation. Results: Thirty-seven kinds of clonal variant were detected from 17 patients with CEL, no recurrent mutation site and hot spot region were found. No pathogenic mutation was detected in 19 patients with PDGFRA rearrangement, but pathogenic mutations of ASXL1, RUNX1 and NRAS were detected from 2 patients with FGFR1 rearrangement who progressed to acute myeloid leukemia and 1 patient with PDGFRB rearrangement who progressed to T lymphoblastic lymphoma, respectively. One hundred and two kinds of clonal abnormalities were detected in 49 patients with HES. The main hot spot mutation regions included: CEBPA Exon1, TET2 Exon3, ASXL1 Exon12, IDH1 Y208C, and FGFR3 L164V. CRRLF2 P224L and PDGFRB R370C point mutations were detected separately in 2 patients with HES who treated with imatinib monotherapy and achieved hematologic remission. Conclusion: The pathogenesis of CEL with PDGFRA, PDGFRB or FGFR1 rearrangement is usually single, and the progression of the disease may involve other driver mutation. A variety of genes with hot mutation regions may be involved in the pathogenesis of HES, and some mutation sites are sensitive to tyrosine kinase inhibitors.
Chronic Disease ; Humans ; Hypereosinophilic Syndrome ; Imatinib Mesylate ; Leukemia ; Receptor, Platelet-Derived Growth Factor alpha ; Receptor, Platelet-Derived Growth Factor beta

OBJECTIVETo explore the clinical and laboratory characteristics of myleodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) with PDGFRβ abnormalities.

METHODSChromosome specimens were prepared directly and/or short-time culture of bone marrow cells. Karyotyping was performed with R-binding technique. Fluorescence in situ hybridization (FISH) was performed using PDGFRβ, PDGFRα, FGFR1 break-apart probes and whole chromosome 5 and 12 painting probes, respectively. The expression of JAK2 V617F was measured with quantitative PCR.

RESULTSThe clinical and hematological findings of 27 patients were compatible with diagnosis of MDS/MPN. PDGFRβ rearrangement was detected in 4 patients with D-FISH, and 2 of which were confirmed as t(5;12) by chromosome painting. PDGFRα, FGFR1 and JAK2 V617F mutation were not detected in these 4 PDGFRβ positive MDS/MPN patients with.

CONCLUSIONSPDGFRβ gene rearrangement may be detected in some MDS/MPN patients. FISH is a convenient and reliable approach to detect PDGFRβ gene.

Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Myeloproliferative Disorders ; genetics ; Neoplasms ; Receptor, Platelet-Derived Growth Factor beta ; genetics

CD146 Antigen ; metabolism ; Humans ; Pericytes ; cytology ; metabolism ; Receptor, Platelet-Derived Growth Factor beta ; metabolism

OBJECTIVE: To explore the relationship between the expression change of cytokines and the wound age during the healing process of rats skin wound. METHODS: Immunohistochemical and image-analysis methods were performed on vital skin wounds(after incision 0.5-168 h am) and postmortem damage(after incision 0.5-6 h pm). RESULTS: The expression of the cytokines PDGF-beta, PDGFR-beta, TGF-beta 1, and bFGF in the epithelial cells was already enhanced since 0.5 h am after damage and their strongest expression reaction was seen at 24-96 h am. In addition, the expression of PDGF-beta, PDGFR-beta, TGF-beta 1 and bFGF was also found in the macrophages and the fibroblasts of the granulation tissue, and the expression changes in the postmortem damage group showed that the skin tissue within 0.5-3 h after incision showed immunohistochemical changes but weakly expression and 3 h thereafter no any change was found. CONCLUSION The expression characteristics of the above mentioned cytokines in wound repair should be related to the wound age and it reminds therefore that they may be used as immunohistochemical criteria for accurate determining the wound age.
Animals ; Cytokines/biosynthesis* ; Female ; Fibroblast Growth Factor 2/biosynthesis* ; Male ; Platelet-Derived Growth Factor/biosynthesis* ; Rats ; Rats, Wistar ; Receptor, Platelet-Derived Growth Factor beta/biosynthesis* ; Skin/metabolism* ; Time Factors ; Transforming Growth Factor beta/biosynthesis* ; Transforming Growth Factor beta1 ; Wound Healing

Animals ; Eosinophilia ; genetics ; pathology ; Gene Rearrangement ; Humans ; Lymphoma ; genetics ; pathology ; Myeloproliferative Disorders ; genetics ; pathology ; Receptor, Fibroblast Growth Factor, Type 1 ; genetics ; Receptor, Platelet-Derived Growth Factor alpha ; genetics ; Receptor, Platelet-Derived Growth Factor beta ; genetics

Myeloid neoplasia with eosinophilia and platelet-derived growth factor receptor beta (PDGFRB) rearrangements is an uncommon Philadelphia-negative myeloproliferative neoplasm. Their most common morphological diagnosis is chronic myelomonocytic leukemia with eosinophilia, which is associated with t(5;12)(q33;p13) and results in the formation of the ETV6-PDGFRB fusion gene. Here, we report a 49-year-old man with a myeloid neoplasm with a PDGFRB rearrangement, who was incidentally diagnosed with hyperleukocytosis and eosinophilia during a health screening. A chromosome analysis of a bone marrow sample revealed 46, XY, t(5;12)(q33;p13), and fluorescence in situ hybridization analysis revealed the PDGFRB gene rearrangement. The patient was treated with imatinib and subsequently achieved complete hematological and molecular remission.
Bone Marrow ; Diagnosis ; Eosinophilia* ; Fluorescence ; Gene Rearrangement ; Humans ; Imatinib Mesylate ; In Situ Hybridization ; Leukemia, Myelomonocytic, Chronic ; Mass Screening ; Middle Aged ; Myeloproliferative Disorders ; Receptor, Platelet-Derived Growth Factor beta* ; Receptors, Platelet-Derived Growth Factor

Myeloid neoplasm with the platelet-derived growth factor receptor beta (PDGFRB) rearrangement is a myeloproliferative neoplasm. Patients with this disease often have prominent eosinophilia or monocytosis and the presence of t(5;12)(q31~33;p12) or a variant translocation with expression of an ETV6-PDGFRB fusion gene or the PDGFRB rearrangement. We report an 82-year-old woman with a myeloid neoplasm, with the PDGFRB rearrangement, who presented with a dry cough, eosinophilia and thrombocytosis. The chromosome study of the bone marrow showed 46,XX,ins(1;5)(q22;q33q13.3), and fluorescence in situ hybridization (FISH) analysis revealed rearrangement of the PDGFRB gene. The patient was successfully treated with low-dose imatinib.
Aged, 80 and over ; Benzamides ; Bone Marrow ; Cough ; Eosinophilia ; Female ; Fluorescence ; Humans ; In Situ Hybridization ; Piperazines ; Pyrimidines ; Receptor, Platelet-Derived Growth Factor beta ; Receptors, Platelet-Derived Growth Factor ; Thrombocytosis ; Imatinib Mesylate

OBJECTIVETo study the expression and significance of platelet derived growth factor (PDGF) and its receptor (PDGFR) in liver tissues of patients with chronic hepatitis fibrosis and liver cirrhosis.

METHODSThe expression, distribution, quantitation, and correlation of PDGF-A, PDGF-B, PDGFR-alpha, PDGFR-beta, and alpha-SMA in the liver tissues were analyzed by immunohistochemical techniques in 21 patients with chronic hepatitis and 42 patients with liver cirrhosis.

RESULTSIn the liver tissues of chronic hepatitis and liver cirrhosis, PDGF and its receptor and alpha-SMA mainly distributed in the fibrotic septa and the infiltration area of inflammation, particularly in branch spindle-shaped cells (activated HSC). The expression of PDGF-B and PDGFR-beta was stronger than that of PDGF-A and PDGFR-alpha with a significant difference between them (P<0.05 approximately 0.01). The expression and distribution of alpha-SMA was basically identical with the expression and distribution of PDGF-A, PDGF-B and PDGFR-alpha, PDGFR-beta and quantitative analysis showed a positive correlation (r=0.606, P<0.001).

CONCLUSIONSPDGF and PDGFR play a key role in liver fibrogenesis and development. The biologic effects of PDGF are elicited through activising HSC. Inhibiting PDGF and its receptor is a new approach to the treatment of liver fibrosis.

Actins ; biosynthesis ; physiology ; Adolescent ; Adult ; Aged ; Female ; Hepatocytes ; metabolism ; Humans ; Liver Cirrhosis ; metabolism ; Male ; Middle Aged ; Muscle, Smooth ; chemistry ; Platelet-Derived Growth Factor ; biosynthesis ; physiology ; Proto-Oncogene Proteins c-sis ; biosynthesis ; physiology ; Receptor, Platelet-Derived Growth Factor alpha ; biosynthesis ; physiology ; Receptor, Platelet-Derived Growth Factor beta ; biosynthesis ; physiology

OBJECTIVETo explore the effect of curcumin on TGF-&beta;2 regulated peroxisome proliferater activated receptor y (PPAR-γ)/platelet derived growth factor &beta; (PDGF-&beta;) signaling pathway in lung fibroblasts of mice.

METHODSC57BL/6 mouse lung fibroblasts were in vitro cultured with TGF-&beta;2, curcumin, or TGF-&beta;2 plus curcumin. The cell proliferation was detected by cell growth counting in the blank control group, low, middle, and high dose curcumin groups (5, 25, 50 μmol/L), the TGF-&beta;2 (10 ng/mL) group, TGF-&beta;2 (10 ng/mL) plus curcumin (5, 25, 50 μmol/L) groups. mRNA expressions of PPAR-γ, platelet-derived growth factor receptor &beta; (PDGFR-&beta;), fibroblast growth factor R1 (FGFR1) were detected using reverse transcription PCR. Protein levels of PPAR-γ and collagen-1 were detected using Western blot and ELISA in the blank control group, the TGF-&beta;2 group, the TGF-&beta;2 (10 ng/mL) plus curcumin 50 μmol/L group.

RESULTSCompared with the blank control group, curcumin 50 μmol/L showed the most significant inhibition on cell proliferation at 48 h and 72 h. Compared with the TGF-&beta;2 group, TGF-&beta;2 (10 ng/mL) plus curcumin 50 mol/L also showed the most significant inhibition on cell proliferation at 48 h and 72 h. Compared with the blank control group, mRNA expressions of PPAR-γ and PDGF-&beta;, as well as protein expression of PPAR-γ increased, the collagen-1 expression also increased in the TGF-&beta;2 group (P < 0.05). Compared with the TGF-&beta;2 group, mRNA expressions of PPAR-γ obviously increased in the TGF-&beta;2 (10 ng/mL) plus curcumin 25 μmol/L group and the TGF-&beta;2 (10 ng/mL) plus curcumin 50 μmol/L group, higher than that in the TGF-&beta;2 (10 ng/mL) plus curcumin 5 [μmol/L group (P < 0.05). mRNA expressions of PPAR-γ was higher in the TGF-&beta;2 (10 ng/mL) plus curcumin 50 μmol/L group than in the TGF-&beta;2 (10 ng/mL) plus curcumin 25 μmol/L group (P < 0.05). mRNA expressions of PDGF-&beta; was lower in TGF-&beta;2 (10 ng/mL) plus curcumin groups than in the TGF-&beta;2 group (P < 0.05). Besides, PDGF-&beta; mRNA expressions were lower in the TGF-&beta;2 (10 ng/mL) plus curcumin 50 μmol/L group than in the TGF-&beta;2 (10 ng/mL) plus curcumin 5 μmol/L group and the TGF-&beta;2 (10 ng/mL) plus curcumin 25 μmol/L group (P < 0.05). There was no statistical difference in FGFR1 mRNA expressions between the TGF-&beta;2 group and 3 TGF-&beta;2 plus curcumin groups (P > 0.05). Compared with the TGF-&beta;2 group, PPAR-γ protein expressions increased and collagen-1 protein expressions decreased in the TGF-&beta;2 (10 ng/mL) plus curcumin 50 μLmol/L group (P < 0.05, P < 0.01).

CONCLUSIONSCurcumin not only could inhibit TGF-&beta;2 induced proliferation of lung fibroblasts, but also could inhibit the synthesis of collagens. These might be associated with up-regulating PPAR-γ expressions and down-regulating PDGF-&beta; expressions. Therefore, curcumin might inhibit the occurrence and developing of lung fibrosis through blocking PPAR-γ/PDGF-&beta; signaling pathway.

Animals ; Cell Proliferation ; Collagen ; Curcumin ; pharmacology ; Fibroblasts ; metabolism ; Lung ; drug effects ; metabolism ; Mice ; Mice, Inbred C57BL ; PPAR gamma ; metabolism ; RNA, Messenger ; Receptor, Platelet-Derived Growth Factor beta ; metabolism ; Signal Transduction ; Transforming Growth Factor beta ; Transforming Growth Factor beta2 ; metabolism

Atypical chronic myeloid leukemia (aCML) is a rare leukemic disorder that shows myelodysplastic and myeloproliferative features simultaneously. The Janus kinase 2 gene V617F mutation (JAK2V617F) in aCML has been the source of much controversy. Some JAK2V617F positive cases have been reported but others observed no JAK2V617F mutation in aCML as defined by WHO classification. Recently, we experienced a case of aCML with JAK2V617F mutation with typical myelodysplastic/myeloproliferative features in peripheral blood and bone marrow aspirates. The karyotype was normal and no BCR/ABL1, PDGFRA or PDGFRB gene rearrangement was noted with FISH analysis. JAK2V617F mutation of the case was identified with amplification refractory mutation system PCR and direct sequencing. We also studied JAK2V617F mutation status in 3 additional cases of previously diagnosed aCML in our institution, but no mutation was identified.
Bone Marrow ; Gene Rearrangement ; Janus Kinase 2 ; Karyotype ; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative ; Myelodysplastic Syndromes ; Myeloproliferative Disorders ; Polymerase Chain Reaction ; Receptor, Platelet-Derived Growth Factor beta