Poor responses to tyrosine kinase inhibitors in a child with precursor B‐cell acute lymphoblastic leukemia with SNX2‐ABL1 chimeric transcript

In addition to BCR, various rare fusion partners for the ABL1 gene have been reported in leukemia. We have identified the fusion gene SNX2‐ABL1 in a pediatric case of acute lymphoblastic leukemia (ALL), which has only once previously been reported in an adult patient. Cytogenetic analysis detected this fusion gene arising from a t(5;9)(q22;q34) translocation. ALL cells carrying a SNX2‐ABL1 fusion exhibited a BCR‐ABL1+ ALL‐like gene expression profile. The patient poorly responded to dasatinib but partially responded to imatinib. Treatment using tyrosine kinase inhibitors requires further investigation to optimize the genotype‐based treatment stratification for patients with SNX2‐ABL1 fusion.     

Suppressor of cytokine signal 3 and IL28 genetic variation predict the viral response to peginterferon and ribavirin

Aim: The aim of this study was to investigate the relationship among the expression of suppressor of cytokine signaling 3 (SOCS 3) in the liver, the SNPs in the IL28B locus, and the outcome of interferon therapy. Methods: Prior to interferon treatment, we immunostained 67 liver specimens from chronic hepatitis C (CHC) patients who were receiving peginterferon alpha‐2b/ribavirin therapy for suppressor of cytokine signaling 3 (SOCS3), and compared the expression of SOCS3, IL28 polymorphisms and other clinical factors between the patients and compared their eventual outcomes. Results: Significant differences between the low SOCS3 group and high SOCS3 group were found in age, as well as in the platelet, transaminase, gamma‐glutamyl transpeptidase levels. The incidence of high SOCS3 was not significantly different between subjects with the TT genotype and the TG genotype (TT : TG = 71%:29%, P = 0.250). In a multivariate analysis, age (≥65 years old) (odds ratio 0.221 [0.120–0.966], P = 0.045), IL28B gene (genotype TT) (odds ratio 5.422 [1.254–23.617], P = 0.024) and SOCS3 (high) (odds ratio 0.308 [0.104–0.948], P = 0.040) were significant predictors of the interferon response. In patients with the TT genotype, those with low SOCS3 immunostaining showed a high sustained virological response (69%), while the sustained virological rate was low (27%) in the patients with high SOCS3 immunostaining. Conclusions: Using a combination of the SOCS3 immunostained area in the liver and the expression of IL28B single nucleotide polymorphisms might be a useful predictor of hepatitis C virus clearance by interferon therapy.     

Expressions of Iba1 and galectin-3 (Gal-3) in thioacetamide (TAA)-induced acute rat liver lesions

Ionized calcium binding adaptor molecule 1 (Iba1) is associated with membrane ruffling and motility of cells. Galectin-3 (Gal-3) is a β-galactoside binding animal lectin, and regulates fibrogenesis probably through transforming growth factor-β1. To evaluate macrophage properties, expressions of Iba1 and Gal-3 were investigated, in relation to macrophages expressing CD68 (ED1; reflecting increased phagocytosis) and CD163 (ED2; implying proinflammatory factor productions) in centrilobular lesions induced in rat livers with thioacetamide (TAA; 300 mg/kg body weight, once intraperitoneally). In agreement with expression patterns of CD68⁺ and CD163⁺ macrophages, cells reacting to Iba1 and Gal-3 were increased in numbers on post-injection (PI) days 1–5, peaking on day 2; thereafter, the positive cells gradually decreased to control levels until PI days 7 and 10. The increased expressions of Iba1 and Gal-3 were confirmed at mRNA levels by the RT-PCR. Double immunofluorescence staining on PI days 2 and 3 demonstrated Iba1 expression in 15–46% of CD68⁺ and CD163⁺ macrophages, and Gal-3 expression in 65–82% of CD68⁺ and CD163⁺ macrophages; Gal-3 expression was observed in 84–93% of Iba1⁺ cells. Interestingly, Gal-3 was also expressed in a small number of α-smooth muscle actin-positive myofibroblasts in fibrotic lesions developed in injured centrilobular areas. These findings indicate that macrophages with various functions can participate in development of liver lesions and resultant fibrosis. Besides CD68 and CD163, Iba1 and Gal-3 immunohistochemistry for macrophages would be useful to analyze the pathogenesis behind developing hepatotoxicity.     

Comparative evaluation of image quality among different detector configurations using area detector computed tomography

The 320-detector row computed tomography (CT) system, i.e., the area detector CT (ADCT), can perform helical scanning with detector configurations of 4-, 16-, 32-, 64-, 80-, 100-, and 160-detector rows for routine CT examinations. This phantom study aimed to compare the quality of images obtained using helical scan mode with different detector configurations. The image quality was measured using modulation transfer function (MTF) and noise power spectrum (NPS). The system performance function (SP), based on the pre-whitening theorem, was calculated as MTF²/NPS, and compared between configurations. Five detector configurations, i.e., 0.5 × 16 mm (16 row), 0.5 × 64 mm (64 row), 0.5 × 80 mm (80 row), 0.5 × 100 mm (100 row), and 0.5 × 160 mm (160 row), were compared using a constant volume CT dose index (CTDI_vol) of 25 mGy, simulating the scan of an adult abdomen, and with a constant effective mAs value. The MTF was measured using the wire method, and the NPS was measured from images of a 20-cm diameter phantom with uniform content. The SP of 80-row configuration was the best, for the constant CTDI_vol, followed by the 64-, 160-, 16-, and 100-row configurations. The decrease in the rate of the 100- and 160-row configurations from the 80-row configuration was approximately 30%. For the constant effective mAs, the SPs of the 100-row and 160-row configurations were significantly lower, compared with the other three detector configurations. The 80- and 64-row configurations were adequate in cases that required dose efficiency rather than scan speed.     

Endoscopic mucosal resection of a rectal malakoplakia in a healthy adult

Malakoplakia in the gastrointestinal tract is rare in healthy young people without underlying disease. Sufficient tissue is required for accurate diagnosis. We describe a malakoplakia that developed in a healthy young woman and was treated by endoscopic mucosal resection (EMR). A 40‐year‐old woman with a history of taking oral contraceptives until one year earlier was referred to our hospital with anal bleeding and constipation. A colonoscopy carried out at our another hospital 18 months earlier disclosed no abnormal findings. Colonoscopy at presentation revealed a yellowish‐white tumor, 5 mm in diameter, in the rectum. The lesion was slightly protruded and had a smooth flat surface, without erosion or ulceration. EMR was carried out for a definitive diagnosis. Histopathological examination showed that the tumor contained granular histiocytes, positive for CD68 and negative forcytokeratin (AE1/AE3). Several histiocytes contained intracytoplasmic round bodies (Michaelis–Gutmann bodies), which reacted positively with periodic acid‐Schiff and calcium (Von Kossa) stains. Intracytoplasmic Escherichia coli (von Hansemann bodies) were identified by Giemsa staining. Based on these results, the tumor in the rectum was diagnosed as a malakoplakia. Following EMR, the patient did not receive further treatment for malakoplakia because she had no symptoms associated with malakoplakia. She has been well for more than 9 months, with no symptoms of disease. Awareness of colorectal malakoplakia is important in patients taking steroids, including oral contraceptives.