Patient: Male, 37Final Diagnosis: PDGFRβ-rearranged myeloid neoplasm with eosinophiliaSymptoms: Night sweats • weight lossMedication: —Clinical Procedure: —Specialty: HematologyObjective:Rare diseaseBackground:PDGFRβ-positive myeloid neoplasms are rare. Marked leukocytosis (over 100×109/L) with marked eosinophilia (over 10%) has been rarely described in myeloid neoplasms associated with PDGFRβ rearrangement.Case report:We report a case of 37-year-old man with myeloid neoplasm associated with PDGFRβ rearrangement who presented with marked eosinophilia of 13.3% and leukocytosis with WBC count of 189×109/L. He was found to have PDGFRβ locus rearrangement at 5q32-33 by fluorescent in situ hybridization (FISH). He responded very well to low-dose imatinib therapy. To the best of our knowledge this degree of hypereosinophilia and leukocytosis in a young adult was reported only once previously. Using low dose therapy in treating this condition has rarely been reported and has not been clearly defined. Our case demonstrated that low dose imatinib therapy can be as effective as high dose imatinib therapy in treating PDGFRβ-positive myeloid neoplasms.Conclusions:The patient presented with very high WBC and eosinophil count rarely reported in a young adult with PDGFRβ-rearranged myeloid neoplasm. The recognition of this rare presentation as a manifestation of PDGFRβ-gene translocation is important, and equally important that low-dose imatinib (100 mg/day) might have the same effect as higher dose imatinib (400 mg/day).
Endogenous erythroid colony (EEC) formation is one of the minor criteria for diagnosing polycythemia vera (PV) according to 2008 WHO diagnostic criteria. But EEC requires bone marrow aspiration and sophisticated laboratory procedures; therefore, practically it is rarely used to diagnose PV. Insulin-like growth factor 1 receptor (IGF-1R) was found to be constitutively phosphorylated and was responsible for the EEC formation in PV; therefore, we measured IGF-1R levels in the peripheral blood of 26 PV patients and compared them with those of 33 patients with secondary polycythemia and 29 normal controls. Among the PV patients, 16 were treated with only phlebotomy, 9 received hydroxyurea, and 1 was treated with ruxolinitinib. We found that PV patients treated with only phlebotomy had significantly higher IGF-1R levels than did those PV patients treated with hydroxyurea or ruxolinitinib. None of the secondary PV patients or normal controls had elevated IGR-1R levels, while 14 of 16 (87%) PV patients had significantly elevated IGF-1R levels. The new 2016 WHO has eliminated EEC as a minor criterion for diagnosing PV, but there are still some cases that cannot be definitively diagnosed by the current criteria. Therefore, we suggest that quantifying the IGF-1R level in peripheral blood by flow cytometry to replace EEC as the minor criterion for diagnosing PV.
International Journal of Case Reports and Images (IJCRI) is an international, peer reviewed, monthly, open access, online journal, publishing high-quality, articles in all areas of basic medical sciences and clinical specialties.Aim of IJCRI is to encourage the publication of new information by providing a platform for reporting of unique, unusual and rare cases which enhance understanding of disease process, its diagnosis, management and clinico-pathologic correlations.IJCRI publishes Review Articles, Case Series, Case Reports, Case in Images, Clinical Images and Letters to Editor.
Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) including essential thrombocythemia(ET), polycythemia vera(PV), and myelofibrosis (MF) have been regarded as a stem cell diseases with malignant clonal proliferation; but recently, inflammatory processes have been proposed as playing found a major role in the pathogenesis of MPN. Toll-like receptors (TLRs) are a family of pattern-recognition receptors that function as key initiators of innate immunity signaling, then induce inflammatorycytokines, and ROS formation. Therefore we measured TLRs, inflammatory cytokines, and ROS in patients with MPN to assess the role of inflammation in MPN. Methods: TLR assay.TLR-2, 4, 7, 9 quantification was performed by immuno-staining of 1×106 mononuclear cells which were incubated with fluorescence-conjugated anti-TLR-2, 4, 7, 9 antibodies and assayed by flow cytometry. Monocytes culture and dendritic cells differentiation.Human monocytes were isolated from human peripheral blood mononuclear cells (PBMNC) using Pan Monocyte Isolation Kit. Isolated monocytes were incubated with IL-4 and GM-CSF in cultures to differentiate to dendric cells . Immature dendritic cells were either left untreated or stimulated with Pam3CSK4. The maturation of dendritic cells was determined by flow cytometry using CD80, CD83, CD11c, and HLA-DR. Multiplex ELISA. Human plasma and cell culture supernatants were analyzed in duplicates by Meso Scale Discovery Multi-Spot Assay system. In total, ten cytokines were assayed: IFN-g, IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and TNF-a. Cell ROS measurement. Cellular ROS was determined by a dichlorofluorescein (DCF) assay. PBMNCs were incubated with 10 µM 2′,7′-dichlorodihydrofluorescein diacetate (carboxy-H2DCFDA) (Life Technology) for 30 min at 37°C. The oxidation of H2DCFDA was measured and analyzed by flowcytometery. Results. 1)TLR2 was the only TLR found to be elevated in PV or ET patients (Fig 1). 2) PlasmaIL-1b levels were elevated in TLR2 high patients than TLR-2 low patients. 3) No difference between TLR-2 high and low patients in the maturation of monocytes to dendritic cells. 4) Monocyte derived dendritic cells with high TLR-2 patientsreleased more IL-8 and TNF-a after Pam3CSK4 stimulation (Fig 2). 5) ROS were more elevated in MF patients than PV, ET patients, and controls (Fig 3). Conclusion. 1) TLR 2 is significantly elevated in PV and some ET patients and TLR-2 high patients were found to have elevated plasma IL-1b,and IL-8, and TNF-α in monocytes-derived dendric cell cultures afterPam3CSK4 stimulation than TLR-2 low patients. This confirms that TLR-2 is deranged in PV and ET. 2) ROS is elevated in MF patients compared to ET and PV patients, or controls. Thus, this study suggests that inflammatory processes likely play a role in the pathogenesis of Ph- MPN through first TLR-2 derangement in PV and ET , then through years of chronic inflammatory process , with the accumulation of more ROS seen in MF, which caused more damage to the DNA resulting more malignant clonal proliferation. A similar phenomenon was observed that in JAK2V617F mutation , allele-burden was observed gradually increased from ET , PV then to MF . Disclosures No relevant conflicts of interest to declare.
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