Myelodysplastic Syndrome Treated by Integrated Chinese and Western Medicine: A Case Report.

Context: Myelodysplastic syndrome (MDS) is a group of highly heterogeneous, malignant clonal diseases derived from hematopoietic stem cells. PD-1 monoclonal antibodies can have a synergistic effect with hypomethylating agents (HMAs), especially for patients with drug resistance to demethylation drugs. TCM in the treatment of MDS can improve hematological indexes, and for some patients, control the proliferation of primitive cells and delay or even block the transformation to leukemia. Objective: The study intended to examine the therapeutic effects of programmed cell death-1 (PD-1) inhibitors and azacitidine combined with the Yisuifang Thick Decoction in the treatment of MDS with older, high-risk patients. Design: The research team performed five prospective case studies. Setting: The study took place at the East Hospital affiliated with Beijing University of Chinese Medicine in Beijing, China. Participants: Participants were five older, high-risk MDS patients at the hospital who received PD-1 and azacitidine combined with Yisuifang Thick Decoction between April 2020 and June 2021. Outcome Measures: The research team measured: (1) treatment duration, (2) curative effects, (3) myelosuppression, (4) immune-related adverse reactions, (5) ending outcomes, and (6) progression-free survival (PFS). Results: The male to female ratio for the five participants was 3:2, and the median age was 69 years, with a range from 62 to 79 years. Four participants had refractory HR-MDS and one had primary MDS. The median treatment duration was 3 months, with a range from 2 to 4 months, and the median progression-free survival (PFS) was 5 months, with a range from 3 to 14 months. All participants achieved a partial response (PR) or a complete remission with incomplete count recovery (CRi) and showed improvement in serological indexes. Conclusions: Older, high-risk MDS patients generally have poor physical conditions, often accompanied by a poor karyotype prognosis and a poor prognosis for survival. Therefore, the combination of PD-1, azacytidine, and Yisuifang Thick Decoction may be an effective way to treat HR-MDS.

Unraveling the therapeutic potential of natural products in the prevention and treatment of leukemia.

Leukemia is a heterogeneous group of hematological malignancies distinguished by differentiation blockage and uncontrolled proliferation of myeloid or lymphoid progenitor cells in the bone marrow (BM) and peripheral blood (PB). There are various types of leukemia in which intensive chemotherapy regimens or hematopoietic stem cell transplantation (HSCT) are now the most common treatments associated with severe side effects and multi-drug resistance in leukemia cells. Therefore, it is crucial to develop novel therapeutic approaches with adequate therapeutic efficacy and selectively eliminate leukemic cells to improve the consequences of leukemia. Medicinal plants have been utilized for ages to treat multiple disorders due to their diverse bioactive compounds. Plant-derived products have been used as therapeutic medication to prevent and treat many types of cancer. Over the last two decades, 50 % of all anticancer drugs approved worldwide are from natural products and their derivatives. Therefore this study aims to review natural products such as polyphenols, alkaloids, terpenoids, nitrogen-containing, and organosulfur compounds as antileukemic agents. Current investigations have identified natural products efficiently destroy leukemia cells through diverse mechanisms of action by inhibiting proliferation, reactive oxygen species production, inducing cell cycle arrest, and apoptosis in both in vitro, in vivo, and clinical studies. Current investigations have identified natural products as suitable promising chemotherapeutic and chemopreventive agents. It played an essential role in drug development and emerged as a possible source of biologically active metabolites for therapeutic interventions, especially in leukemia. DATA AVAILABILITY: Data will be made available on request.

The antileukemic effects of saffron (Crocus sativus L.) and its related molecular targets: A mini review.

Saffron (Crocus sativus L.), and its main constituents, crocin, and crocetin have shown promising effects as an antileukemic agent in animal models and cell culture systems. Saffron retards the growth of cancer cells via inhibiting nucleic acid synthesis and enhancing antioxidative system. It can induce apoptosis and chemosensitivity via inhibiting multidrug resistance proteins. Saffron also induces differentiation pathways via inhibiting promyelocytic leukemia/retinoic acid receptor-α, histone deacetylase1, and tyrosyl DNA phosphodiesterase-1 as well. The present review highlights the most recent findings on the antileukemic effects of saffron and its underlying molecular targets. The emerging evidence suggests that saffron has a selective toxicity effect against leukemic cells while is safe for the normal cells.

Coffee and tea consumption and risk of leukaemia in an adult population: A reanalysis of the Italian multicentre case-control study.

BACKGROUND: Coffee and tea are the most frequently consumed beverages in the world. Their potential effect on the risk of developing different types of malignancies has been largely investigated, but studies on leukaemia in adults are scarce. METHODS: The present investigation is aimed at evaluating the potential role of regular coffee and tea intake on the risk of adult leukaemia by reanalysing a large population based case-control study carried out in Italy, a country with a high coffee consumption and a low use of green tea. Interviewed subjects, recruited between 1990 and 1993 in 11 Italian areas, included 1771 controls and 651 leukaemia cases. Association between Acute Myeloid Leukaemia (AML), Acute Lymphoid Leukaemia, Chronic Myeloid Leukaemia, Chronic Lymphoid Leukaemia, and use of coffee and tea was evaluated by standard logistic regression. Odds Ratios (OR) were estimated adjusting for the following potential confounders: gender, age, residence area, smoking habit, educational level, previous chemotherapy treatment, alcohol consumption and exposure to electromagnetic fields, radiation, pesticides and aromatic hydrocarbons. RESULTS: No association was observed between regular use of coffee and any type of leukaemia. A small protective effect of tea intake was found among myeloid malignancies, which was more evident among AML (OR=0.68, 95%CI: 0.49-0.94). However, no clear dose-response relation was found. CONCLUSION: The lower risk of leukaemia among regular coffee consumers, reported by a few of previous small studies, was not confirmed. The protective effect of tea on the AML risk is only partly consistent with results from other investigations.

Green tea consumption and glutathione S-transferases genetic polymorphisms on the risk of adult leukemia.

PURPOSE: Green tea may have a beneficial role of inhibiting leukemia. Glutathione S-transferases (GSTs) are known to detoxify certain carcinogens. We investigated the roles of green tea consumption and polymorphisms of GSTM1, GSTT1 and GSTP1 on the risk of adult leukemia, and to determine whether the associations varied within GSTs genotypes. METHODS: A multicenter case-control study was conducted in China, 2008-2013. It comprised 442 incident, hematologically confirmed adult leukemia cases and 442 outpatient controls, individually matched to cases by gender, birth quinquennium and study site. Data were collected by face-to-face interview using a validated questionnaire. Genetic polymorphisms were assayed by PCR. RESULTS: An inverse association between green tea consumption and adult leukemia risk was observed. Compared with non-tea drinkers, the adjusted odds ratios (95 % confidence intervals) were 0.50 (0.27-0.93), 0.31 (0.17-0.55) and 0.53 (0.29-0.99) for those who, respectively, consumed green tea >20 years, ≥2 cups daily and dried tea leaves >1000 g annually. In assessing the associations by GSTs genotypes, risk reduction associated with green tea consumption was stronger in individuals with the GSTT1-null genotype (OR 0.24; 95 % CI 0.11-0.53) than GSTT1-normal carriers (OR 0.67; 95 % CI 0.42-1.05; P interaction = 0.02). GSTM1 and GSTP1 did not significantly modify the inverse association of leukemia with green tea. CONCLUSIONS: The results suggest that regular daily green tea consumption may reduce leukemia risk in Chinese adults regardless of GSTM1 and GSTP1 polymorphic status. The association between green tea and adult leukemia risk varied with GSTT1 genotype and highlights further study.

Childhood Leukemia and Primary Prevention.

Leukemia is the most common pediatric cancer, affecting 3800 children per year in the United States. Its annual incidence has increased over the last decades, especially among Latinos. Although most children diagnosed with leukemia are now cured, many suffer long-term complications, and primary prevention efforts are urgently needed. The early onset of leukemia-usually before 5 years of age-and the presence at birth of "pre-leukemic" genetic signatures indicate that pre- and postnatal events are critical to the development of the disease. In contrast to most pediatric cancers, there is a growing body of literature-in the United States and internationally-that has implicated several environmental, infectious, and dietary risk factors in the etiology of childhood leukemia, mainly for acute lymphoblastic leukemia, the most common subtype. For example, exposures to pesticides, tobacco smoke, solvents, and traffic emissions have consistently demonstrated positive associations with the risk of developing childhood leukemia. In contrast, intake of vitamins and folate supplementation during the preconception period or pregnancy, breastfeeding, and exposure to routine childhood infections have been shown to reduce the risk of childhood leukemia. Some children may be especially vulnerable to these risk factors, as demonstrated by a disproportionate burden of childhood leukemia in the Latino population of California. The evidence supporting the associations between childhood leukemia and its risk factors-including pooled analyses from around the world and systematic reviews-is strong; however, the dissemination of this knowledge to clinicians has been limited. To protect children's health, it is prudent to initiate programs designed to alter exposure to well-established leukemia risk factors rather than to suspend judgment until no uncertainty remains. Primary prevention programs for childhood leukemia would also result in the significant co-benefits of reductions in other adverse health outcomes that are common in children, such as detriments to neurocognitive development.

Breastfeeding, Other Early Life Exposures and Childhood Leukemia and Lymphoma.

Childhood cancer incidence increases and although rare, it is a leading cause of mortality. Leukemia and lymphoma comprise 40% of all cancers in children but little is known of their etiology. In this study, we examined the associations of breastfeeding and other early life exposures with childhood leukemia and lymphoma. A population-based case-control study carried out in 2011-2013 comprised mothers of 190 incidents (2005-2013) of leukemia/lymphoma cases aged 1-19 yr at diagnosis and 384 population-based controls. Interviews based on a computerized structured questionnaire were conducted with the mothers. Multivariate logistic regression models adjusted for potential confounders assessed the association between breastfeeding patterns and childhood leukemia/lymphoma. Ever breastfeeding category was associated with a 64% decreased risk for childhood leukemia/lymphoma lsqb;odds ratio (OR) = 0.36, 95% confidence interval (CI): 0.22, 0.60lrqb; and similar trends, with a dose-response effect, were observed for any breastfeeding (exclusive and/or partial) category for 6, 12, and 18+ mo. Other infant exposures associated with cancer risk were child iron supplementation (OR = 0.39, 95% CI: 0.26, 0.59), pet ownership (OR = 0.50, 95% CI: 0.33, 0.78), paternal smoking (OR = 1.93, 95% CI: 1.18, 3.15), and having older siblings (OR = 1.18, 95% CI: 1.05, 1.33). Breastfeeding-a controllable and modifiable exposure-is inversely associated with risk for childhood leukemia and lymphoma with a dose-response effect.

Beta-Sitosterol: A Promising but Orphan Nutraceutical to Fight Against Cancer.

All the currently available cancer therapeutic options are expensive but none of them are safe. However, traditional plant-derived medicines or compounds are relatively safe. One widely known such compound is beta-sitosterol (BS), a plant derived nutrient with anticancer properties against breast cancer, prostate cancer, colon cancer, lung cancer, stomach cancer, ovarian cancer, and leukemia. Studies have shown that BS interfere with multiple cell signaling pathways, including cell cycle, apoptosis, proliferation, survival, invasion, angiogenesis, metastasis and inflammation. Most of the studies are incomplete partly due to the fact that BS is relatively less potent. But the fact that it is generally considered as nontoxic, the opposite of all currently available cancer chemo-therapeutics, is missed by almost all research communities. To offset the lower efficacy of BS, designing BS delivery for "cancer cell specific" therapy hold huge potential. Delivery of BS through liposome is one of such demonstrations that has shown to be highly promising. But further research did not progress neither in the field of drug delivery of BS nor in the field on how BS mediated anticancer activities could be improved, thus making BS an orphan nutraceutical. Therefore, extensive research with BS as potent anticancer nutraceutical is highly recommended.

Immunoprophylactic potential of wheat grass extract on benzene-induced leukemia: An in vivo study on murine model.

OBJECTIVES: Wheat grass (Triticum aestivum) is a gift of nature given to mankind. A number of scientific research on wheatgrass establishes its anticancer and antioxidant potential. Current work was focused to determine antileukemic effect of wheat grass. MATERIALS AND METHODS: The commercial wheatgrass powder was extracted with 95% of methanol. Methanol extract of wheat grass was studied for acute oral toxicity as per revised Organization for Economic Cooperation and Development Guidelines number 423. Leukemia was successfully induced in Wister rats by intravenous injection of benzene. The blood was collected and analyzed for hematological parameters. Phagocytotic activity of the extract was determined. RESULTS: Phytochemical screening revealed the presence of flavonoids, phenolics, carbohydrates, and amino acids. From acute toxicity studies, it was found that the methanol extract of wheatgrass was safe up to a dose level of 2000 mg/kg of body weight. Outcomes of hematological parameters in various experimental groups of murine model demonstrated antileukemic effect of extract. Methanol extract of wheatgrass aroused the process of phagocytosis of killed Candida albicans and also demonstrated a significant chemotactic activity at all tested concentrations. CONCLUSION: In the current work, methanol extract of wheat grass demonstrated antileukemic potential that might be due to the presence of flavonoids and polyphenolics in it. Further isolation, structural characterization of active constituents is necessary to extrapolate the mechanism of action.

Tea consumption and leukemia risk: a meta-analysis.

Epidemiologic findings concerning the association between tea consumption and leukemia risk yielded mixed results. We aimed to investigate the association by performing a meta-analysis of all available studies. One cohort studies and six case-control studies with 1,019 cases were identified using PubMed, Web of Science, and EMBASE. We computed summary relative risks (RRs) and 95 % confidence intervals (CIs) using random effect model applied to the relative risk associated with ever, moderate, or highest drinkers vs. non/lowest drinkers. Subgroup analyses were performed based on country (China and USA). Compared with non/lowest drinkers, the combined RR for ever drinkers was 0.76 (95 % CI=0.65-0.89). In subgroup analyses, significant inverse associations were found for both China and USA studies. The summary RR was 0.57 (95 % CI=0.41-0.78) for highest drinkers. Same results were only found in China studies. No significant associations were found for moderate drinkers in overall analysis or in subgroup analyses. There was some evidence of publication bias. In conclusion, this meta-analysis suggests a significant inverse association of high tea consumption and leukemia risk. Results should be interpreted cautiously given the potential publication bias.

An anthocyanin-rich extract from Hibiscus sabdariffa linnaeus inhibits N-nitrosomethylurea-induced leukemia in rats.

A previous study reported that anthocyanins from roselle (Hibiscus sabdariffa L.) showed significant anticancer activity in human promyelocytic leukemia cells. To explore the antitumor effect of anthocyanin, a roselle bioactive polyphenol in a rat model of chemical-induced leukemia was assayed. Anthocyanin extract of roselle (Hibiscus anthocyanins, HAs) was supplemented in the diet (0.1 and 0.2%). This study was carried out to evaluate the protective effect of HAs on N-nitrosomethylurea (NMU)-induced leukemia of rats. The study employed male Sprague-Dawley rats (n = 48), and leukemia was induced by intravenous injection of 35 mg kg(-1) body weight of NMU dissolved in physiologic saline solution. The rats were divided into four groups (n = 12): control, NMU only, and HAs groups that received different doses of HAs (0.1 and 0.2%) daily, orally, after NMU injection. After 220 days, the animals were killed, and the following parameters were assessed: morphological observation, hematology examination, histopathological assessment, and biochemical assay. When compared with the NMU-only group, HAs significantly prevented loss of organ weight and ameliorated the impairment of morphology, hematology, and histopathology. Treatment with HAs caused reduction in the levels of AST, ALT, uric acid, and MPO. Also, the results showed that oral administration of HAs (0.2%) remarkably inhibited progression of NMU-induced leukemia by approximately 33.3% in rats. This is the first report to demonstrate that the sequential administration of HAs followed by NMU resulted in an antileukemic activity in vivo.

Hispolon from Phellinus linteus induces G0/G1 cell cycle arrest and apoptosis in NB4 human leukaemia cells.

Hispolon (a phenolic compound isolated from Phellinus linteus) has been shown to possess strong antioxidant, anti-inflammatory, anticancer, and antidiabetic properties. In this study, we investigated the antiproliferative effect of hispolon on human hepatocellular carcinoma NB4 cells using the MTT assay, DNA fragmentation, DAPI (4, 6-diamidino-2-phenylindole dihydrochloride) staining, and flow cytometric analysis. Hispolon inhibited the cellular growth of NB4 cells in a dose-dependent manner through the induction of cell cycle arrest at G0/G1 phase measured using flow cytometric analysis and apoptotic cell death, as demonstrated by DNA laddering. Exposure of NB4 cells to hispolon-induced apoptosis-related protein expressions, such as the cleavage form of caspase 3, caspase 8, caspase 9, poly (ADP ribose) polymerase, and the proapoptotic Bax protein. Western blot analysis showed that the protein levels of extrinsic apoptotic proteins (Fas and FasL), intrinsic related proteins (cytochrome c), and the ratio of Bax/Bcl-2 were increased in NB4 cells after hispolon treatment. Hispolon-induced G0/G1-phase arrest was associated with a marked decrease in the protein expression of p53, cyclins D1, and cyclins E, and cyclin-dependent kinases (CDKs) 2, and 4, with concomitant induction of p21waf1/Cip1 and p27Kip1. We conclude that hispolon induces both of extrinsic and intrinsic apoptotic pathways in NB4 human leukemia cells in vitro.

Potential of olive oil phenols as chemopreventive and therapeutic agents against cancer: a review of in vitro studies.

Olive oil is a common component of Mediterranean dietary habits. Epidemiological studies have shown how the incidence of various diseases, including certain cancers, is relatively low in the Mediterranean basin compared to that of other European or North America countries. Current knowledge indicates that the phenolic fraction of olive oil has antitumor effects. In addition to the ability to be chemopreventive, with its high antioxidant activity, the antitumor effects of olive oil phenols (OO-phenols) has been studied because of their capacity to inhibit proliferation and promote apoptosis in several tumor cell lines, by diverse mechanisms. This review will summarize and discuss the most recent relevant results on the antitumor effect of OO-phenols on leukemia tumor cells, colorectal carcinoma cells, and breast cancer (BC) cells. In particular, very recent data will be reported and discussed showing the molecular signaling pathways activated by OO-phenols in different histopathological BC cell types, suggesting the potential use of OO-phenols as adjuvant treatment against several subsets of BC. Data summarized here represent a good starting point for more extensive studies for better insight into the molecular mechanisms induced by OO-phenols and to increase the availability of chemopreventive or therapeutic drugs to fight cancer.

Population versus hospital controls for case-control studies on cancers in Chinese hospitals.

BACKGROUND: Correct control selection is crucial to the internal validity of case-control studies. Little information exists on differences between population and hospital controls in case-control studies on cancers in Chinese hospital setting. METHODS: We conducted three parallel case-control studies on leukemia, breast and colorectal cancers in China between 2009 and 2010, using population and hospital controls to separately match 540 incident cases by age, gender and residency at a 1:1 ratio. Demographic and lifestyle factors were measured using a validated questionnaire in face-to-face interview. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained using conditional logistic regression analyses. RESULTS: The two control groups had closely similar exposure distributions of 15 out of 16 factors, with the only exception being that hospital controls were less likely to have a BMI ≥ 25 (OR = 0.71, 95% CI: 0.54, 0.93). For exposure of green tea drinking, the adjusted ORs (95% CIs) comparing green tealeaves intake ≥ 1000 grams annually with non-drinkers were 0.51 (0.31, 0.83) and 0.21 (0.27, 0.74) for three cancers combined, 0.06 (0.01, 0.61) and 0.07 (0.01, 0.47) for breast cancer, 0.52 (0.29, 0.94) and 0.45 (0.25, 0.82) for colorectal cancer, 0.65 (0.08, 5.63) and 0.57 (0.07, 4.79) for leukemia using hospital and population controls respectively. CONCLUSIONS: The study found that hospital controls were comparable with population controls for most demographic characteristics and lifestyle factors measured, but there was a slight difference between the two control groups. Hospital outpatients provide a satisfactory control group in hospital-based case-control study in the Chinese hospital setting.

The quinolone derivative CHM-1 inhibits murine WEHI-3 leukemia in BALB/c mice in vivo.

CHM-1 [2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-one] is a quinolone derivative that has been reported to induce apoptosis and inhibit invasion of cancer cells. However, there is no available information to address the effects of CHM-1 on leukemia cells in vivo. Therefore, the present study examined the effects of CHM-1 using a mouse model of leukemia. We established leukemia in mice by injecting WEHI-3 cells into BALB/c mice. Mice were then treated with or without CHM-1 (5 and 10 mg/kg). CHM-1 promoted the total survival rate of leukemic mice and these effects were dose-dependent. CHM-1 increased body weight and decreased spleen weight, but did not affect liver weight. The levels of cell markers Mac-3 and CD11b were reduced by CHM-1, indicating that the differentiation of macrophage precursor cells was inhibited. Levels of CD3 and CD19 were induced by CHM-1, suggesting that the differentiation of precursors of T and B cells was promoted in PBMC. Results of the present study indicate that CHM-1 has an inhibitory effect on leukemia induced in mice in vivo and warrants further study as to the mechanisms and effects in other types of cancer.

Anti-leukemia activity of a bacterial toxin with natural specificity for LFA-1 on white blood cells.

The oral bacterium, Aggregatibacter actinomycetemcomitans, produces a leukotoxin (LtxA) that is specific for white blood cells (WBCs) from humans and Old World primates by interacting with lymphocyte function antigen-1 (LFA-1) on susceptible cells. To determine if LtxA could be used as a therapeutic agent for the treatment of WBC diseases, we tested the in vitro and in vivo anti-leukemia activity of the toxin. LtxA kills human malignant WBC lines and primary leukemia cells from acute myeloid leukemia patients, but healthy peripheral blood mononuclear cells (PBMCs) are relatively resistant to LtxA-mediated cytotoxicity. Levels of LFA-1 on cell lines correlated with killing by LtxA and the toxin preferentially killed cells expressing the activated form of LFA-1. In a SCID mouse model for human leukemia, LtxA had potent therapeutic value resulting in long-term survival in LtxA-treated mice. Intravenous infusion of LtxA into a rhesus macaque resulted in a drop in WBC counts at early times post-infusion; however, red blood cells, platelets, hemoglobin and blood chemistry values remained unaffected. Thus, LtxA may be an effective and safe novel therapeutic agent for the treatment of hematologic malignancies.

Mifepristone treatment improves length and quality of survival of mice with spontaneous leukemia.

BACKGROUND: Mifepristone was found to suppress expression of the progesterone-induced blocking factor (PIBF). Progesterone-induced blocking factor suppresses natural killer cell activity. The objective of the present study was to determine if treatment of mice with spontaneous murine lymphocyte leukemia with the progesterone receptor antagonist mifepristone could improve length and quality of life. MATERIALS AND METHODS: Sixty-one mice were gavaged with mifepristone and 33 controls with olive oil. Quality of life was determined by body conditioning score (BCS). Treatment was initiated when the mice were 6 months old. RESULTS: Within 2 weeks of therapy only 11.4% of the mifepristone treated mice died vs. about 50% of controls. The BCS was 5 (highest quality) in 82% of treated mice vs. 11% of controls after 2 weeks of therapy. CONCLUSION: Mifepristone therapy should be further evaluated for treating leukemia and lymphoma.

Antineoplastic effects of n-3 polyunsaturated fatty acids in combination with drugs and radiotherapy: preventive and therapeutic strategies.

Many data support the beneficial effect of n-3 polyunsaturated fatty acids (PUFAs) as chemopreventive and chemotherapeutic agents in the treatment of several chronic pathologies including cancer. Different molecular mechanisms have been proposed to explain their effects, including alterations in arachidonic acid oxidative metabolism and metabolic conversion of n-3 PUFAs to novel discovered bioactive derivatives; modification of oxidative stress; changes in cell membrane fluidity and structure and altered metabolism and function of membrane proteins. Considerable knowledge has been recently gathered on the possible beneficial effects of n-3 PUFAs administered in combination with different antineoplastic drugs and radiotherapy against melanoma, leukemia, neuroblastoma, and colon, breast, prostate, and lung cancer. The efficacy of these combinations has been demonstrated both in vivo and in vitro, and clinical trials have also been conducted. The aim of this review is to analyze all the n-3 PUFA combinations investigated so far, their efficacy, and the possible molecular mechanisms involved. It would be highly auspicable that the detailed analysis of the literature in this field could further support the common use of n-3 PUFAs in combination with other chemopreventive agents and warrant more clinical investigations designed to test the effectiveness of n-3 PUFA treatments coupled with conventional antineoplastic therapies.

Licochalcone A is a potent inhibitor of TEL-Jak2-mediated transformation through the specific inhibition of Stat3 activation.

Aberrant activation of Jak/Stat signaling causes a number of hematopoietic disorders and oncogenesis, and therefore the effective inhibitors of the Jak/Stat signaling pathway may be therapeutically useful. TEL-Jak2 gene fusion, which has been identified in human leukemia, encodes a chimeric protein endowed with constitutive tyrosine kinase activity. Expression of TEL-Jak2 protects Ba/F3 cells from IL-3 withdrawal-induced apoptotic cell death and leads to IL-3-independent growth. However, its mechanisms remain to be only partially understood. Here, we first found that Licochalcone A, one of the flavonoids isolated from the root of Glycyrrhiza inflate, inhibited TEL-Jak2-mediated cell proliferation and survival in the absence of IL-3. Licochalcone A failed to inhibit the activity of TEL-Jak2, however, this induced apoptosis of TEL-Jak2-transformed cells with a much lower concentration in the absence of IL-3 than in the presence of IL-3. Interestingly, Licochalcone A significantly inhibited the phosphorylation and nuclear localization of Stat3, which is essential for TEL-Jak2-induced cell transformation. These data suggest that Licochalcone A is a specific inhibitor for Stat3 and would be employed for the treatment of various diseases caused by disorders of the Jak/Stat pathway.

[A case-control study on green tea consumption and the risk of adult leukemia].

OBJECTIVE: To investigate whether green tea consumption can reduce the risk of adult leukemia. METHODS: A hospital-based matched case-control study was conducted in 2005 - 2006. We recruited 107 confirmed leukemia cases and 110 inpatient controls with orthopedic disease without leukemia or other malignancy matched on gender, age and hospitals that patients stayed. Related information were gathered on quantity, duration and frequency of tea consumption, demographic characteristics, exposure to radiation and occupational hazards, medications, using a validated questionnaire by face-to-face interview. Univariate and multivariate unconditional logistic regression analysis were used to estimate odds ratios (ORs) and associated 95% confidence intervals (CIs) with SPSS 11.5 software. RESULTS: Compared with non-tea-drinkers, the OR of those who consumed green tea was 0.58 (95% CI:0.34-1.00, P< 0.05) under univariate statistical analysis. The OR was 0.52 ( 95% CI: 0.28- 0.98, P = 0.04), using logistic regression to count for age, gender, residential area, smoking, level of education, exposure to radiation, benzene and organo-phosphorus. Compared with non-drinkers, the risk of adult leukemia declined with increasing quantity, duration, and frequency of green tea consumption. Tests for trend on dose-response was statistically significant (P < 0.01). CONCLUSION: A higher consumption of green tea seemed to be associated with a declined risk of adult leukemia. Tea consumption might be of help to human health planning projects.