Inhibition of Nrf2-mediated glucose metabolism by brusatol synergistically sensitizes acute myeloid leukemia to Ara-C.

Chemotherapy resistance remains to be the primary barrier to acute myeloid leukemia (AML) treatment failure. Nuclear factor-erythroid 2-related factor 2 (Nrf2) has been well established as a truly pleiotropic transcription factor. Inhibition of Nrf2 function increases the sensitivity of various chemotherapeutics and overcomes chemoresistance effectively.

CDK6 Is a Potential Prognostic Biomarker in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a threatening hematological malignant disease in which new successful approaches in therapy are needed. Cyclin-dependent kinase 6 (), a regulatory enzyme of the cell cycle that plays an important role in leukemogenesis and the maintenance of leukemia stem cells (LSC), has the potential to predict the prognosis of AML. By analyzing public databases, we observed that the messenger RNA (mRNA) levels of were significantly overexpressed in AML cell lines and non-acute promyelocytic leukemia (non-APL) AML patients when compared to healthy donors.

Chidamide acts on the histone deacetylase-mediated miR-34a/Bcl-2 axis to regulate NB4 cell line proliferation and apoptosis.

Acute promyelocytic leukemia (APL), a biologically and clinically distinct variant of acute myelogenous leukemia, is characterized by the fusion of the N-terminus of promyelocytic leukemia protein to the C terminus of retinoic acid receptor alpha, mostly due to chromosomal translocation t(15;17). Chidamide, a synthetic analogue of MS-275 identified from a group of benzamide-type compounds, has been found to have efficient anticancer activity in basic and clinical research studies. However, the concrete role and underlying mechanism of Chidamide in the treatment of APL has not been well characterized.

Roles of hsa-miR-12462 and SLC9A1 in acute myeloid leukemia.

MicroRNAs (miRNAs) play important roles in cell proliferation, differentiation, and survival and may be useful for acute myeloid leukemia (AML) diagnosis and prognosis. In this study, we defined a novel miRNA, hsa-miR-12462, through small RNA sequencing of the bone marrow (BM) cells from 128 AML patients. Overexpression of hsa-miR-12462 in AML cells (U937 and HL-60) significantly decreased their growth rate when compared with those of the wild-type and MOCK controls.

Down-regulating NQO1 promotes cellular proliferation in K562 cells via elevating DNA synthesis.

Background: NQO1 protein acts as a cellular protective system, on account of its role as a quinone reductase and redox regulator. Nonetheless, new NQO1 roles are emerging-including its regulation of the cellular proliferation of many tumor cells-and this enzyme has been found to relate to the incidence of various diseases, including chronic myeloid leukemia. However, the mechanisms through which NQO1 influences leukemia progression remain unclear.

Effects of Trough Concentration and Solute Carrier Polymorphisms on Imatinib Efficacy in Chinese Patients with Chronic Myeloid Leukemia.

Purpose: We investigated the relationship between imatinib trough concentrations and genetic polymorphisms with efficacy of imatinib in Chinese patients with chronic myeloid leukemia (CML).

Methods: There were 171 eligible patients. Peripheral blood samples were collected from 171 eligible patients between 21 and 27 hours after the last imatinib administration.

Population pharmacokinetic and pharmacogenetics of imatinib in Chinese patients with chronic myeloid leukemia.

Aim: This study aimed to establish a population pharmacokinetic (PPK) model in Chinese patients with chronic myeloid leukemia, and to quantify the effects of pharmacogenetics on pharmacokinetic parameters of imatinib.

Methods: A total of 229 plasma concentrations from 170 patients were analyzed. Nonlinear mixed effect model was used to establish the PPK model.

Association of genetic polymorphisms in genes involved in Ara-C and dNTP metabolism pathway with chemosensitivity and prognosis of adult acute myeloid leukemia (AML).

Background: Cytarabine arabinoside (Ara-C) has been the core of chemotherapy for adult acute myeloid leukemia (AML). Ara-C undergoes a three-step phosphorylation into the active metabolite Ara-C triphosphosphate (ara-CTP). Several enzymes are involved directly or indirectly in either the formation or detoxification of ara-CTP.

A validated UPLC-MS/MS method for simultaneous determination of imatinib, dasatinib and nilotinib in human plasma.

A sensitive, rapid, simple and economical ultra-performance liquid chromatography-tandem mass spectrometric method (UPLC-MS/MS) was developed and validated for simultaneous determination of imatinib, dasatinib and nilotinib in human plasma using gliquidone as internal standard (IS). Liquid-liquid extraction method with ethyl acetate was used for sample pre-treatment. The separation was performed on an Xtimate Phenyl column using isocratic mobile phase consisting of A (aqueous phase: 0.

High Expression of AHSP, EPB42, GYPC and HEMGN Predicts Favorable Prognosis in FLT3-ITD-Negative Acute Myeloid Leukemia.

Background/aims: Acute myeloid leukemia (AML) is a heterogeneous clonal disease and patients with AML who harbor an FMS-like tyrosine kinase 3 (FLT3) mutation present several dilemmas for the clinician. This study aims to identify novel targets for explaining the dilemmas.

Methods: We analyzed four microarray gene expression profiles to investigate changes in whole genome expression associated with FLT3-ITD mutation.

Trough concentration and ABCG2 polymorphism are better to predict imatinib response in chronic myeloid leukemia: a meta-analysis.

Aim: The present study aimed to conduct a series of meta-analyses to investigate the influence of imatinib trough concentration (C), as well as ABCB1 and ABCG2 polymorphisms, on the clinical response in patients with chronic myeloid leukemia (CML).

Methods: A literature search was conducted using the PubMed and Cochrane electronic databases to locate relevant papers from 2003 onward. Then, an initial meta-analysis of 14 studies involving 2184 patients was conducted to understand the effect of imatinib mesylate (IM) C on clinical outcome in CML patients.

Role of HMGB1 in regulation of STAT3 expression in CD4(+) T cells from patients with aGVHD after allogeneic hematopoietic stem cell transplantation.

Treg/Th17 balance plays a critical role in maintaining immune homeostasis of acute graft-versus-host disease (aGVHD) patients. STAT3 is an important factor involved in the instability of Treg and the promotion of Th17. HMGB1 is a cytokine mediator of inflammation and an important chromatin protein regulating gene transcription.

Inactivation of PTEN increases ABCG2 expression and the side population through the PI3K/Akt pathway in adult acute leukemia.

Both the occurrence and recurrence of acute leukemia (AL) might suggest the presence of leukemia stem cells. Side population (SP) cells, exhibiting stem cell-like properties, express ABCG2 (breast cancer resistance protein [BCRP]). This study revealed that over-expression of ABCG2 in Jurkat and HL60 cells led to an increased SP fraction, up-regulated levels of phosphorylated-PI3K and phosphorylated-Akt, and enhanced drug resistance, all of which could be attenuated by treatment with either the PI3K inhibitor LY294002 or the mTOR inhibitor rapamycin.

[Role of Lyn kinase in imatinib-resistant chronic myelogenous leukemia].

This study was aimed to explore the role of Lyn kinase in imatinib-resistant CML. Lyn, BCR/ABL fusion gene and chromosomes were detected in 76 CML patients being divided into imatinib-resistant, newly diagnosed and effective groups, and then the expression of Lyn was compared and the relationship between Lyn and clinical characteristics, BCR/ABL fusion gene and chromosomes were analyzed. The results indicated that all the 76 CML patients and 10 normal persons expressed Lyn.

[Expression of DNA-dependent protein kinase catalytic subunit in adult acute leukemia and its significance].

This study was aimed to explore the expression of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) in adult acute leukemia and its correlation with clinical characteristics, karyotype and prognosis. Indirect immunofluorescent cytometry was used to detect the expression of DNA-PKcs in bone marrow mononuclear cells of 105 patients with acute leukemia before chemotherapy and 41 of them after 2 cycles of chemotherapy. Cytogenetic data were obtained from 26 of them by R band karyotypic analysis.

[Expression of angiotensin-II type 1 receptor at1 mRNA in myeloid leukemia].

This study was aimed to explore the expression level of angiotensin-II type 1 receptor (AT1) mRNA in bone marrow of myeloid leukemic patients, and its correlation with the proportion of leukemia cells in samples and Hb, WBC, Plt counting in peripheral blood. 51 samples, including 36 AML, 7 CML, and 8 samples of non-malignant hematological diseases as control group were collected. The expression of at1 mRNA was detected by real time-PCR; the expression levels of at1 gene in AML and CML groups were relatively quantitatively analyzed by using 2(-ΔΔCT) and were compared with control group.

Hypothesizing that histone deacetylase inhibitors can be used to reverse multiple drug resistance.

It is well known that the mechanism of action of chemotherapeutic drugs and their ability to induce multidrug resistance (MDR) are of relevance to cancer treatment. Although MDR is a multifactorial process, the main obstacle is the expression of multidrug-efflux pumps that lowers the intracellular drug levels. P-glycoprotein (P-gp) is the longest identified efflux pump.

Correlation between MDR1 methylation status in the promoter region and MDR1 genetic polymorphism in 194 healthy Chinese Han subjects.

Aims: To investigate the correlation between the methylation status in the MDR1 promoter region and the MDR1 genetic polymorphism.

Methods: A total of 194 unrelated subjects (105 men and 89 women) with a median age of 26 years were enrolled in this study. DNA was extracted and PCR-RFLP was performed for C1236T, C3435T and G2677T/A polymorphism genotyping.

Meta-analysis of the effect of MDR1 C3435T polymorphism on cyclosporine pharmacokinetics.

The published data revealed conflicting results of the polymorphism of MDR1 exon 26 SNP C3435T on the pharmacokinetics of cyclosporine; thus, the aim was to conduct a meta-analysis of significant magnitude to investigate the influence of SNP C3435T on the pharmacokinetics of cyclosporine. A literature search was conducted to locate the relevant papers by using the PubMed electronic source from 1997 and onwards. The pharmacokinetic parameters, including AUC(0-4), AUC(0-12), AUC(0-inf), C(max), CL/F and trough concentration (C(0)), were extracted and a meta-analysis was performed by using Stata version 9.

[Therapeutic effect of priming induction regimen of CAG for newly diagnosed acute myeloid leukemia in elderly patients].

Objective: To evaluate the clinical efficacy and toxicity of priming induction regimen of CAG for newly diagnosed acute myeloid leukemia (AML) in elderly patients.

Methods: Seventy-five patients with newly diagnosed AML were divided into 2 groups: 34 were treated with priming induction regimen CAG and the other 41 were treated with 2 classic routine chemotherapy regimens including pirarubicin+cytarabine (TA) and homoharringtonine+cytarabine (HA). All patients had a 14 day interval between the 2 courses of chemotherapy.

[Effect of recombinant human interleukin 11 on the platelet after hematopoietic stem cell transplantation in patients with leukemia].

Objective: To explore the effect and toxicity profile of recombinant human interleukin 11(rhIL-11) on the platelet after hematopoietic stem cell transplantation in patients with leukemia.

Methods: Twenty-four patients with acute or chronic leukemia treated by allogeneic peripheral blood stem cell transplantation (PBSCT) were randomly divided into a test group and a control group. The patients in the test group were treated with rhIL-11 since the 13th day after PBSCT (1.