3D Neuromorphic Hardware with Single Thin-Film Transistor Synapses Over Single Thin-Body Transistor Neurons by Monolithic Vertical Integration.

Neuromorphic hardware with a spiking neural network (SNN) can significantly enhance the energy efficiency for artificial intelligence (AI) functions owing to its event-driven and spatiotemporally sparse operations. However, an artificial neuron and synapse based on complex complementary metal-oxide-semiconductor (CMOS) circuits limit the scalability and energy efficiency of neuromorphic hardware. In this work, a neuromorphic module is demonstrated composed of synapses over neurons realized by monolithic vertical integration. The synapse at top is a single thin-film transistor (1TFT-synapse) made of poly-crystalline silicon film and the neuron at bottom is another single transistor (1T-neuron) made of single-crystalline silicon. Excimer laser annealing (ELA) is applied to activate dopants for the 1TFT-synapse at the top and rapid thermal annealing (RTA) is applied to do so for the 1T-neuron at the bottom. Internal electro-thermal annealing (ETA) via the generation of Joule heat is also used to enhance the endurance of the 1TFT-synapse without transferring heat to the 1T-neuron at the bottom. As neuromorphic vision sensing, classification of American Sign Language (ASL) is conducted with the fabricated neuromorphic module. Its classification accuracy on ASL is ≈92.3% even after 204 800 update pulses.

Phenolic compounds, antioxidant capacity, and α-amylase and α-glucosidase inhibitory activity of ethanol extracts of perilla seed meal.

Perilla frutescens is a medicinal herb that is commonly cultivated in Asian countries. Perilla seed is extensively pressed for cooking oil extraction. However, phenolic chemicals are still abundant in pressed perilla seed meal (PSM), which was previously thought to be useless after oil extraction. In our study, PSM was extracted using five solvents (water and 25%, 50%, 75%, and 100% ethanol) based on different ethanol concentrations, and its antioxidant activity, phenolic compounds, and inhibitory effects against key enzymes related to diabetes mellitus were evaluated. The 75% ethanol extract had higher phenolic (105.58 mg GAE/g DW) and flavonoid (66.52 mg QE/g DW) contents and showed better antioxidant and inhibitory effects against α-glucosidase and α-amylase. Analysis of the phenolic compounds of the five extracts by HPLC indicated the presence of apigenin, rosmarinic acid, benzoic acid, caffeic acid, and vanillic acid. Therefore, because of its high antioxidant activity and inhibitory capacity against enzymes relevant to diabetes, the 75% ethanol extract of perilla seed meal has the most potential to be used as a functional or nutraceutical food in the prevention and treatment of oxidation and diabetes.

Efficacy and Safety of Yukgunja-Tang for Patients with Cancer-related Anorexia: A Randomized, Controlled Trial, Pilot Study.

OBJECTIVE: The purpose of this study is both to estimate the efficacy and the safety of Yukgunja-tang (YGJT) and to establish evidence for the use of herbal medicines in the management of patients with cancer-related anorexia. METHODS: We enrolled 40 patients with cancer-related anorexia. The enrolled participants were randomly allocated to 2 groups: the control group (n = 20), which received nutrition counseling, and the treatment group (n = 20), which received nutrition counseling and was administered YGJT at twice a day for 4 weeks (a total of 56 times @ 3.0 g each time). The primary outcome of this study was the score on the anorexia/cachexia subscale (ACS) of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT). The secondary outcomes were the FAACT score with the ACS score excluded, the score on the Visual Analog Scale (VAS) for appetite, and the results on laboratory tests regarding appetite, such as leptin, tumor necrosis factors (TNF-α), interleukin-6 (IL-6), and ghrelin. All variables related to the safety assessment, such as vital signs, electrocardiography results, laboratory test results (complete blood cell count, chemistry, urine test), and adverse events, were documented on the case report form (CRF) at every visit. RESULT: The difference in the primary outcome, that is, the score on the anorexia/cachexia subscale (ACS) of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT), between the control and the treatment groups was statistically significant (P = .023) as was the difference in the FAACT scores with the ACS score excluded, a secondary outcome, between the 2 groups; however, no statistically significant differences were noted in the scores on the VAS or the levels of leptin, TNF-α, IL-6, and ghrelin. In addition, no significant differences in the numbers and the types of adverse events or in the results on the laboratory tests between the control and the treatment groups were recorded. CONCLUSION: These results obtained in this research confirmed the efficacy and the safety of using YGJT as a herb-medicine treatment option for patients with cancer-related anorexia.

Near-infrared-emitting nanoparticles activate collagen synthesis via TGFß signaling.

Research efforts towards developing near-infrared (NIR) therapeutics to activate the proliferation of human keratinocytes and collagen synthesis in the skin microenvironment have been minimal, and the subject has not been fully explored. Herein, we describe the novel synthesis Ag2S nanoparticles (NPs) by using a sonochemical method and reveal the effects of NIR irradiation on the enhancement of the production of collagen through NIR-emitting Ag2S NPs. We also synthesized Li-doped Ag2S NPs that exhibited significantly increased emission intensity because of their enhanced absorption ability in the UV-NIR region. Both Ag2S and Li-doped Ag2S NPs activated the proliferation of HaCaT (human keratinocyte) and HDF (human dermal fibroblast) cells with no effect on cell morphology. While Ag2S NPs upregulated TIMP1 by only twofold in HaCaT cells and TGF-ß1 by only fourfold in HDF cells, Li-doped Ag2S NPs upregulated TGF-ß1 by tenfold, TIMP1 by 26-fold, and COL1A1 by 18-fold in HaCaT cells and upregulated TGF-ß1 by fivefold and COL1A1 by fourfold in HDF cells. Furthermore, Ag2S NPs activated TGF-ß1 signaling by increasing the phosphorylation of Smad2 and Smad3. The degree of activation was notably higher in cells treated with Li-doped Ag2S NPs, mainly caused by the higher PL intensity from Li-doped Ag2S NPs. Ag2S NPs NIR activates cell proliferation and collagen synthesis in skin keratinocytes and HDF cells, which can be applied to clinical light therapy and the development of anti-wrinkle agents for cosmetics.

Plumbagin Suppresses Pulmonary Fibrosis via Inhibition of p300 Histone Acetyltransferase Activity.

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial lung disease with a poor prognosis similar to that of malignancy. The causes of IPF are not clearly known, and there is no effective therapy to date. In this study, the natural compound plumbagin, which was isolated from Plumbago rosea root extract, was screened for p300 inhibitory activity. Plumbagin specifically inhibited the activity of p300 toward histone acetyltransferases. Plumbagin treatment significantly suppressed transforming growth factor-ß-induced profibrotic target-gene expression and proliferation of fibroblast cell lines. Moreover, plumbagin significantly inhibited bleomycin-induced pulmonary fibrosis in mice. Taken together, these data demonstrate the inhibitory effects of plumbagin on lung fibrosis and its promise as a therapeutic agent for IPF.

Revision of Laboratory Testing Guidelines for Initial Diagnosis of Hematologic Neoplasms

Low relapse rate of urinary tract infections from extended-spectrum beta-lactamase-producing bacteria in young children.

BACKGROUND: Extended-spectrum-beta-lactamase (ESBL)-producing bacteria are an increasingly important cause of urinary tract infections (UTIs) worldwide. We evaluated clinical characteristics and associated risk factors of UTIs in young children according to ESBL-producing status and relapse rates. METHODS: All urinary culture results in patients younger than 2 years old were assessed, and only children with febrile UTIs from gram-negative bacterial infections were reviewed. RESULTS: Of 845 episodes evaluated, 146 (17.3%) were caused by ESBL-positive bacteria. Significant differences were observed in previous UTIs, use of antibiotics or history of hospitalization within previous 3 months, and underlying urinary abnormalities between the ESBL UTI and non-ESBL UTI groups. After 2 weeks of treatment completion, UTI relapse occurred in 2.7% of children in the ESBL group and 1.1% of children in the non-ESBL group (P = 0.13). In the ESBL UTI group, relapse rate was not significantly different between patients treated with susceptible antibiotics and those treated with non-susceptible but clinically effective antibiotics. CONCLUSIONS: Previous history of UTI, antibiotic treatment, or hospitalization within previous 3 months and underlying disease are risk factors for ESBL UTI in children under 24 months of age. However, relapse rate was < 3% regardless of in vitro susceptibility of the treating antibiotics, as long as the antibiotics were clinically effective. We cautiously propose that we may continue the use of initial empirical antibiotics when a definite clinical response is observed, although further study is necessary to confirm the findings of this study.

Precise tuning of the glyoxylate cycle in Escherichia coli for efficient tyrosine production from acetate.

BACKGROUND: Acetate is one of promising feedstocks owing to its cheap price and great abundance. Considering that tyrosine production is gradually shifting to microbial production method, its production from acetate can be attempted to further improve the economic feasibility of its production. RESULTS: Here, we engineered a previously reported strain, SCK1, for efficient production of tyrosine from acetate. Initially, the acetate uptake and gluconeogenic pathway were amplified to maximize the flux toward tyrosine. As flux distribution between glyoxylate and TCA cycles is critical for efficient precursor supplementation, the activity of the glyoxylate cycle was precisely controlled by expression of isocitrate lyase gene under different-strength promoters. Consequently, the engineered strain with optimal flux distribution produced 0.70 g/L tyrosine with 20% of the theoretical maximum yield which are 1.6-fold and 1.9-fold increased values of the parental strain. CONCLUSIONS: Tyrosine production from acetate requires precise tuning of the glyoxylate cycle and we obtained substantial improvements in production titer and yield by synthetic promoters and 5' untranslated regions (UTRs). This is the first demonstration of tyrosine production from acetate. Our strategies would be widely applicable to the production of various chemicals from acetate in future.

Inhibitory effects of Euphorbia supina on Propionibacterium acnes-induced skin inflammation in vitro and in vivo.

BACKGROUND: Euphorbia supina (ES) plant has been used as treatment for inflammatory conditions. The antibacterial effect and the anti-inflammatory mechanism of ES for Propionibacterium (P.) acnes-induced inflammation in THP-1 cells and acne animal model remain unclear. Therefore, the objective of the present study was to determine the antibacterial and anti-inflammatory activities of ES against P. acnes, the etiologic agent of skin inflammation. METHOD: The antibacterial activities of ES were tested with disc diffusion and broth dilution methods. Cytotoxicity of ES at different doses was evaluated by the MTT assay. THP-1 cells were stimulated by heat-killed P. acnes in the presence of ES. The pro-inflammatory cytokines and mRNA levels were measured by ELISA and real-time-PCR. MAPK expression was analyzed by Western blot. The living P. acnes was intradermally injected into the ear of BLBC/c mice. Subsequently, chemical composition of ES was analyzed by liquids chromatography-mass spectrometry (LC-MS). RESULT: ES had stronger antibacterial activity against P. acnes and inhibitory activity on lipase. ES had no significant cytotoxicity on THP-1 cells. ES suppressed the mRNA levels and production of IL-8, TNF-a, IL-1ß in vitro. ES inhibited the expression levels of pro-inflammatory cytokines and the MAPK signaling pathway. Ear thickness and inflammatory cells were markedly reduced by ES treatment. Protocatechuic acid, gallic acid, quercetin, and kaempferol were detected by LC-MS analysis in ES. CONCLUSIONS: Our results demonstrate antibacterial and anti-inflammatory activities of ES extract against P. acnes. It is suggested that ES extract might be used to treatment anti-inflammatory skin disease.

Etiology and clinical feature of oral allergy syndrome in children

PURPOSE: Oral allergy syndrome (OAS) is a unique allergic reaction to fresh fruits or vegetables, which is caused by cross-reactivity between foods and pollens. This study was conducted to investigate the clinical feature of OAS and relevant pollen allergens as well as the association between them in Korean children. METHODS: This single-center study included 290 children who were sensitized to pollens at Severance Hospital, and the clinical characteristics of children with and without OAS were compared. A multicenter study included 97 children who were diagnosed with OAS at 3 hospitals between January 2008 and June 2014. The details of clinical features were collected by retrospective medical record reviews using a standardized case report form. The relevant pollen allergens were identified by skin prick tests and/or serum specific IgE levels. RESULTS: The most commonly sensitized allergen was Japanese hop in pollen-sensitized children. Children with OAS were most commonly sensitized to birch and oak, and 12.4% of the pollen-sensitized children had OAS in the single center. The number of children who were newly diagnosed with OAS has increased over the past 7 years. The most common causative food of OAS was apple. More than 60% of patients with OAS had oral allergic reactions to multiple foods. CONCLUSION: OAS may be relatively common in pollen-sensitized children. OAS should be considered in children with allergic disease and sensitization to pollens.

Aronia Berry Extract Ameliorates the Severity of Dextran Sodium Sulfate-Induced Ulcerative Colitis in Mice.

Inflammatory bowel disease, including Crohn's disease and ulcerative colitis (UC), is a group of inflammatory conditions of the colon and small intestine. UC is a chronic inflammatory disorder of the colon and rectum that includes intervals of acute exacerbation. Although recent studies have suggested that proinflammatory cytokines might have initiated the inflammatory responses in UC, its etiology remains unclear. Aronia berries are rich in dietary polyphenols such as phenolic acids, anthocyanins, flavonoids, and proanthocyanidins with various health benefits, including antioxidant, anti-inflammatory, and antiaging activities. The objective of this study was to determine whether Aronia berry can be an effective intervention for the treatment of UC. BALB/c mice were administered 5% dextran sulfate sodium (DSS) to induce UC. They were then given Aronia berry extracts at concentrations of 10 or 100 mg/kg. During the induction of UC, the expression levels of nuclear factor-kappa B were increased in colonic epithelial cells and immune cells, leading to increased proinflammatory cytokine levels. Aronia berry extract significantly improved the clinical signs of DSS-induced UC, including body weight loss, colon length shortening, and disease activity index increase, with histological markers of colon injury. Furthermore, oral administration of Aronia berry extract inhibited prostaglandin E2 production in DSS-induced colitis and decreased the levels of nitric oxide, interleukin-6, and tumor necrosis factor-α in lipopolysaccharide-stimulated macrophages. These results suggest that Aronia berry extract could efficiently ameliorate clinical signs and inflammatory mediators of UC. Therefore, Aronia berry might be a promising natural treatment for UC.

Age-Based Causes and Clinical Characteristics of Immediate-Type Food Allergy in Korean Children

PURPOSE: Age-based causes and clinical characteristics of immediate-type food allergy (FA) have not been sufficiently studied. Therefore, we investigated age-dependent clinical profiles of FA in Korean children through an extensive multicenter investigation. METHODS: Using a case report form developed by the authors, a retrospective medical record review was performed of patients (0-18 years old) diagnosed with immediate-type FA between September 2014 and August 2015 in 14 tertiary hospitals in Korea. RESULTS: A total of 1,353 children and adolescents, 93% younger than 7 years, were enrolled in the present study, and 1,661 cases of immediate-type FA were recorded in these patients. The 7 major causative foods were cow's milk (28.1%), hen's eggs (27.6%), wheat (7.9%), walnuts (7.3%), peanuts (5.3%), buckwheat (1.9%), and shrimps (1.9%). Categorizing the patients into 4 age groups revealed that the most common causative food was different for each age group: cow's milk (<2 years), walnuts (2–6 years), walnuts (7–12 years), and buckwheat (13-18 years). The onset time of symptoms was less than 10 minutes in 49%, between 10 and 30 minutes in 17%, and between 30 minutes and 2 hours in 34% of cases. Food-induced anaphylaxis was reported in 506 (30.5%) out of 1,661 cases, and the 7 major causes of food-induced anaphylaxis was cow's milk (27.5%), hen's eggs (21.9%), wheat (11.3%), walnuts (10.5%), peanuts (5.9%), buckwheat (4.2%), and pine nuts (3.0%). The proportion of anaphylaxis was highest in the patients allergic to buckwheat (67.7%), followed by those allergic to pine nuts (57.7%), walnuts (43.8%), wheat (43.5%), and peanuts (34.1%). CONCLUSIONS: The 5 major causative foods of immediate-type FA in Korean children were cow's milk, hen's eggs, wheat, walnuts, and peanuts. The distribution of causative foods was considerably distinctive according to different age groups. Anaphylaxis was reported in 30.5% of immediate-type FA cases.

Vitamin D levels in allergic rhinitis: a systematic review and meta-analysis.

BACKGROUND: We aimed to systematically review observational studies investigating the relationship between vitamin D levels and allergic rhinitis (AR). METHODS: Studies were selected if they evaluated the relationship between vitamin D levels and AR, and included studies that evaluated other allergic conditions if those studies also contained data on AR. We assessed the incidence and prevalence of AR according to vitamin D levels and compared vitamin D levels in patients with AR to levels in controls. RESULTS: Nineteen studies were selected. Of these, only seven focused solely on AR; 10 studies evaluated the other allergic diseases as well as AR; and two studies evaluated asthma primarily, but also included data on patients with AR. The pooled odds ratios (ORs) for the incidence of AR according to vitamin D levels were not statistically significant for either children or adults. Lower vitamin D levels were associated with a higher AR prevalence only in children (pooled OR [95% confidence interval (CI)], 0.75 [0.58, 0.98]). The pooled mean vitamin D level in patients with AR was lower than that of controls only in children (pooled means difference [95% CI], -7.63 [-13.08, -2.18]). CONCLUSIONS: Prior vitamin D levels were not related to developing AR, but lower vitamin D levels were associated with a higher AR prevalence only in children. There is insufficient evidence to support vitamin D supplementation for AR prevention. However, physicians should consider evaluating patients for vitamin D deficiency during AR management, especially in children.

A Multicenter Retrospective Case Study of Anaphylaxis Triggers by Age in Korean Children

PURPOSE: Although anaphylaxis is recognized as an important, life-threatening condition, data are limited regarding its triggers in different age groups. We aimed to identify anaphylaxis triggers by age in Korean children. METHODS: We performed a retrospective review of medical records for children diagnosed with anaphylaxis between 2009 and 2013 in 23 secondary or tertiary hospitals in South Korea. RESULTS: A total of 991 cases (mean age=5.89±5.24) were reported, with 63.9% involving patients younger than 6 years of age and 66% involving male children. Food was the most common anaphylaxis trigger (74.7%), followed by drugs and radiocontrast media (10.7%), idiopathic factors (9.2%), and exercise (3.6%). The most common food allergen was milk (28.4%), followed by egg white (13.6%), walnut (8.0%), wheat (7.2%), buckwheat (6.5%), and peanut (6.2%). Milk and seafood were the most common anaphylaxis triggers in young and older children, respectively. Drug-triggered anaphylaxis was observed more frequently with increasing age, with antibiotics (34.9%) and nonsteroidal anti-inflammatory drugs (17.9%) being the most common causes. CONCLUSIONS: The most common anaphylaxis trigger in Korean children was food. Data on these triggers show that their relative frequency may vary by age.

Eco-friendly approach towards green synthesis of zinc oxide nanocrystals and its potential applications.

In the present study, we investigated a novel green route for synthesis of zinc oxide (ZnO) nanocrystals using Prunus × yedoensis Matsumura leaf extract as a reducing agent without using any surfactant or external energy. Standard characterization studies were carried out to confirm the obtained product using UV-Vis spectra, SEM-EDS, FTIR, TEM, and XRD. In addition, the synthesized ZnO nanocrystals were coated onto fabric and leather samples to study their bacteriostatic effect against odor-causing bacteria Brevibacterium linens and Staphylococcus epidermidis. Zinc oxide nanocrystal-coated fabric and leather showed good activity against both bacteria.

Effect of heavy metals on acdS gene expression in Herbaspirillium sp. GW103 isolated from rhizosphere soil.

This study aimed to understand the influence of heavy metals on 1-aminocyclopropane-1-carboxylate deaminase activity (ACCD) and acdS gene expression in Herbaspirillium sp. GW103. The GW103 strain ACCD activity decreased in cells grown in a medium supplemented with Pb and As, whereas cells grown in medium supplemented with Cu showed increase in enzyme activity. The GW103 strain produced 262.2 ± 6.17 µmol of α-ketobutyrate per milligram of protein per hour during ACC deamination at 25 °C after 24 h incubation. Using a PCR approach, an acdS coding-gene of 1.06 kbp was amplified in isolate GW103, showing 92% identity with Herbaspirillum seropedicae SmR1 acdS gene. Real time quantitative polymerase chain reaction results indicate that the acdS expression rate was increased (7.1-fold) in the presence of Cu, whereas it decreased (0.2- and 0.1-fold) in the presence of As and Pb.

Bioleaching characteristics, influencing factors of Cu solubilization and survival of Herbaspirillum sp. GW103 in Cu contaminated mine soil.

This study was aimed at assess the potential of diazotrophic bacteria, Herbaspirillum sp. GW103, for bioleaching of Cu in mine soil. The strain exhibited resistance to As (550mgL(-1)), Cu (350mgL(-1)), Zn (300mgL(-1)) and Pb (200mgL(-1)). The copper resistance was further confirmed by locating copA and copB genes. The survival of the isolate GW103 during bioleaching was analyzed using green fluorescent protein tagged GW103. Response surface methodology based Box-Behnken design was used to optimize the physical and chemical conditions for Cu bioleaching. Five significant variables (temperature, incubation time, CaCO3, coconut oil cake (COC), agitation rate) were selected for the optimization. Second-order polynomials were established to identify the relationship between Cu bioleaching and variables. The optimal conditions for maximum Cu bioleaching (66%) were 30°C, 60h of incubation with 1.75% of CaCO3 and 3% COC at 140rpm. The results of Cu sequential extraction studies indicated that the isolate GW103 leached Cu from ion-exchangeable, reducible, strong organic and residual fractions. Obtained results point out that the isolate GW103 could be used for bioleaching of Cu from mine soils.

The safety of influenza vaccination in children with egg allergy

PURPOSE: Although influenza vaccine contains some residual egg protein (ovalbumin), recent studies have been reported that the influenza vaccine is even safe for patients with egg allergy. The object of this study was to assess the safety of influenza vaccination and estimate the risk factors of allergic reactions to influenza vaccination in children with egg allergy. METHODS: The medical records of 108 children were reviewed retrospectively, those were diagnosed as egg allergy at Department of Pediatrics in Severance Children's Hospital between January 2006 and December 2011. All of them were vaccinated with very low ovalbumin concentration (< or =0.12 microg/mL). Patients were vaccinated in graded doses by the international guideline. Subjects without allergic reactions to influenza vaccine among egg allergy patients were recruited as control subjects. RESULTS: Only 12 subjects of patients had adverse reactions to influenza vaccination. There were no significant relationships between adverse reactions to influenza vaccine and their own history of other allergy, history of breast feeding or graded vaccination. The egg allergy symptoms or egg-specific IgE levels were not associated with adverse reactions to influenza vaccination. CONCLUSION: These results show that patients with egg allergy may have adverse reactions with influenza vaccine, but severe adverse reactions are rare as general population. Therefore, the patients with egg allergy can be safe vaccinated with influenza vaccine, regardless of severity of allergic reaction after egg ingestion or methods of vaccination.

A case of therapy-related acute lymphoblastic leukemia with t(11;19)(q23;p13.3) and MLL/MLLT1 gene rearrangement.

Therapy-related ALL (t-ALL) is a rare secondary leukemia that develops after chemotherapy and/or radiotherapy for primary malignancies. Chromosomal 11q23 abnormalities are the most common karyotypic alterations in t-ALL. The t(11;19)(q23;p13) aberration is extremely rare and has not been confirmed at the molecular genetic level. Here, we report a case of t-ALL with t(11;19)(q23;p13.3) and MLL-MLLT1 (alias ENL) gene rearrangement confirmed by cytogenetic analysis, multiplex reverse transcription-PCR (multiplex RT-PCR), and DNA sequencing in a patient who had undergone treatment for breast cancer. A 40-yr-old woman developed acute leukemia 15 months after undergoing 6 cycles of adjuvant chemotherapy (doxorubicin 60 mg/m² and cyclophosphamide 600 mg/m²), radiation therapy (dose, 5,900 cGy), and anticancer endocrine therapy with tamoxifen. The complete blood cell counts and bone marrow examination showed increased blasts and the blasts showed B lineage immunophenotype (positive for CD19, CD34, and cytoplasmic CD79a). Cytogenetic analysis revealed the karyotype 47,XX,+X,t(11;19)(q23;p13.3)[4]/46,XX[16]. FISH analyses, multiplex RT-PCR, and DNA sequencing confirmed the MLL-MLLT1 gene rearrangement. The patient underwent induction chemotherapy with fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD) and achieved complete remission. Subsequently, she underwent consolidation chemotherapy, but died of brain ischemia in the pons and the region of the middle cerebral artery. To our knowledge, this is the first case report of t-ALL with t(11;19)(q23;p13.3) and the MLL-MLLT1 gene rearrangement.

A Case of Therapy-related Acute Lymphoblastic Leukemia with t(11;19)(q23;p13.3) and MLL/MLLT1 Gene Rearrangement / 대한진단검사의학회지

Therapy-related ALL (t-ALL) is a rare secondary leukemia that develops after chemotherapy and/or radiotherapy for primary malignancies. Chromosomal 11q23 abnormalities are the most common karyotypic alterations in t-ALL. The t(11;19)(q23;p13) aberration is extremely rare and has not been confirmed at the molecular genetic level. Here, we report a case of t-ALL with t(11;19)(q23;p13.3) and MLL-MLLT1 (alias ENL) gene rearrangement confirmed by cytogenetic analysis, multiplex reverse transcription-PCR (multiplex RT-PCR), and DNA sequencing in a patient who had undergone treatment for breast cancer. A 40-yr-old woman developed acute leukemia 15 months after undergoing 6 cycles of adjuvant chemotherapy (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2), radiation therapy (dose, 5,900 cGy), and anticancer endocrine therapy with tamoxifen. The complete blood cell counts and bone marrow examination showed increased blasts and the blasts showed B lineage immunophenotype (positive for CD19, CD34, and cytoplasmic CD79a). Cytogenetic analysis revealed the karyotype 47,XX,+X,t(11;19)(q23;p13.3)[4]/46,XX[16]. FISH analyses, multiplex RT-PCR, and DNA sequencing confirmed the MLL-MLLT1 gene rearrangement. The patient underwent induction chemotherapy with fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD) and achieved complete remission. Subsequently, she underwent consolidation chemotherapy, but died of brain ischemia in the pons and the region of the middle cerebral artery. To our knowledge, this is the first case report of t-ALL with t(11;19)(q23;p13.3) and the MLL-MLLT1 gene rearrangement.