The success of ATRA and ATO in APL treatment furuishes the first model of molecular target-based induction of differentiation and apoptosis.Two drugs all target PML-RARα oncoprotein through different moieties and induce APL cells differentiation and apoptosis.In acute myeloid leukemia M2b,we reveal that gain-of-function of C-kit coexists with persistent AML1-ETO,suggesting that abnormal C-kit may serve as a therapeutic target in AML L-M2b Oridonin becomes a potential candidate target drug which specifically degrades AML1-ETO protein. Experiment in vitro proves the combinatorial effectiveness of imatinib and cytarabin in the treatment of chronic myelogenous leukemia(CML).Imatinib is an inhibitor of abnormal protein tyrosine kinases activity. While arsenic agent triggers the degradation of bcr-abl, and combination of the two drugs in treating CML leads to a better outcome.

Metabolomics is one of the branches of systems biology,which employs nuclear magnetic resonance and mass spectrometry technologies to detect the abnormal metabolites from a variety of body fluids. Study of various molecules and their functions may help to find the disease-related early metabolic marker clusters,understand the molecular mechanism of pathogenesis,which provides broad prospects for the early diagnosis and individualized treatment of malignant tumors.

With the development of the research in human genomics, it is well known that genetic polymorphisms(mainly single nucleotide polymorphisms) of the genes encoding drug-metabolizing enzymes, transporters, receptors and other drug target proteins are relative to interindividual differences in the efficacy and toxicity of many medications. On the basis of functional genomics and molecular pharmacology, pharmacogenomics is elucidating the inherited nature of these differences in drug response mainly by means of analyzing the genetic variations of DNA and monitoring the gene expression pattern. It can not only improve disease diagnosis and predict the potential drug response but also speed up drug discovery and its development which will be instructive for clinical drug therapy ultimately.
Drug Therapy ; methods ; Genome, Human ; Humans ; Pharmacogenetics ; methods

Objective To study the pharmacokinetics and metabolism of arsenic trioixide (As2O3) and its main side effects.Method As2O3 was administered intravenously at the dose of 10 mg per day for the treatment of 8 relapsed acute promyelocytic leukemia (APL) patients. The arsenic content was measured by Gas-phase chromotography. Results The plasma maximal concentration (Cpmax) was 0.94±0.37 mg/L (±s), time to peak concentration (Tp) was 4 hours, plasma distribution half-time (t1/2α) and elimination half-time (t1/2β) were 0.89±0.29 hours and 12.13±3.31 hours, respectively. Apparent distribution volume (Vc) was 3.83±0.45 L, system clearance (CLs) was 1.43±0.17 L/h, and area under curve (AUC) was 7.25±0.97 mg*h/L. The continuous administration of As2O3 did not alter its pharmacokinetic behaviors. During As2O3 treatment, 24-hour arsenic content in urine accounted for 1%-8% of the dialy dose (10 mg). When arsenic accumulation in hair and nail increased continuously, the peak concentration could be five to seven-fold higher than that of pre-treatment. Importantly, arsenic contents in both urine and hair or nail declined gradually after drug withdrawal. No bone marrow suppression or severe organ-impairment was found.Conclusion As2O3 is a relatively safe and effective remedy in the treatment of patients with relapsed APL, in spite of certain degree of arsenic accumulation in some tissues.

OBJECTIVETo report two myelodysplatic syndromes (MDS) patients with t(3; 5) (q25; q34).

METHODSChromosome specimens were prepared by short-term culture of bone marrow cells. Karyotype analysis was performed by R banding technique, chromosome painting (fluorescence in situ hybridization, FISH) by using whole chromosome 3 and 5 probes in case 1.

RESULTSThe clinical and hematological findings were compatible with diagnosis of MDS. Karyotype analysis showed that both patients had identical t(3; 5) (q25; q34) translocation. A reciprocal translocation between chromosomes 3q and 5q was proved by FISH in one patient.

CONCLUSIONSt(3; 5) translocation is a rare chromosome abnormality specifically associated with MDS and frequently displays trilineage dysplasia. Chromosome painting technique is a reliable tool for detecting this translocation.

Adolescent ; Adult ; Antigens, CD ; analysis ; Chromosomes, Human, Pair 3 ; Chromosomes, Human, Pair 5 ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Leukocytes, Mononuclear ; classification ; immunology ; Male ; Myelodysplastic Syndromes ; genetics ; physiopathology ; Translocation, Genetic

To investigate the leukemogenic potential of PML-RARalpha fusion protein in vivo, hCG-PML-RARalpha transgene was constructed using molecular cloning technique and hCG-PML-RARalpha transgenic mice were generated. The genotype and phenotype of hCG-PML-RARalpha transgenic mice were analyzed by PCR, RT-PCR, morphology of peripheral blood and bone marrow cells, and pathological examination of spleen, liver and bone marrow. As a result, acute promyelocytic leukemia was developed in 3 hCG-PML-RARalpha transgenic mice in 1 - 5 months. The results demonstrated that PML-RARalpha fusion protein plays a crucial role in leukemogenesis.

OBJECTIVETo set up the technical system of multiplex fluorescence in situ hybridization M-FISH and to explore its application in detection of the complex chromosome abnormalities in leukemia.

METHODSThe complex chromosome abnormalities of two leukemia patients were analyzed by the combination use of classical cytogenetics, chromosome painting (CP), FISH and M-FISH.

RESULTSIn a case of acute lymphoblastic leukemia-L2, the complex karyotype: 46,XY,der(2)t(2;9),der(9)t(9;12;22) was identified by M-FISH, which was detected as 46,XY,der(9)t(9;12) by classical cytogenetics; In a case of acute monocytic leukemia-M5, the complex chromosome abnormalities: 46,XY,der(2)t(2;17), der(10)t(10;11;17), der(11)t(11;?) was revealed by M-FISH, which was confirmed by CP and FISH, and mixed lineage leukemia (MLL) gene was also found involved in this complex chromosome translocation.

CONCLUSIONM-FISH was proved to be a powerful tool to examine the complicated karyotypes and hopefully to elucidate nearly all chromosomal aberrations in leukemia and other cancers.

Chromosome Aberrations ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; genetics

Objective　To investigate the response of multiple myeloma (MM) cells to arsenic trioxide (As2O3) and their possible mechanisms. Methods　Two MM-derived cell lines RPMI8226 and U266 cells were used as in vitro models. Cell apoptosis was assessed by morphology, flow cytometry, and DNA gel electrophoresis. Mitochondrial transmembrane potentials (△Ψm) were evaluated by measuring cellular Rhodamine 123 staining intensity. Protein expression was analyzed using Western blot. Results　Zero point one to 0.5?μmol/L As2O3 inhibited cell proliferation and 2.0?μmol/L As2O3 induced cell apoptosis, while 1.0?μmol/L As2O3 inhibited proliferation with a weak degree of apoptosis induction in RPMI8226 and U266 cell lines. As2O3-induced apoptosis was accompanied by mitochondrial transmembrane potentials (△Ψm) collapse and caspase-3 activation in the presence of intact membrane. Glutathione depleter buthionine sulfoximine enhanced, while disulfide bond-reducing agent dithiothreitol partially antagonized As2O3-induced △Ψm collapse and apoptosis in MM cells. All-trans retinoic acid (ATRA) could also induce apoptosis in RPMI8226 cells, but it did not show any cooperative effects with As2O3. Conclusion　As2O3 exerts apoptosis-inducing and growth-inhibiting effects on MM cells, and mitochondrium is a pivotal and common target of As2O3 for apoptosis induction.

Since the outbreak of the COVID-19 pandemic in early December 2019, 81 174 confirmed cases and 3242 deaths have been reported in China as of March 19, 2020. The Chinese people and government have contributed huge efforts to combat this disease, resulting in significant improvement of the situation, with 58 new cases (34 were imported cases) and 11 new deaths reported on March 19, 2020. However, as of March 19, 2020, the COVID-19 pandemic continues to develop in 167 countries/territories outside of China, and 128 665 confirmed cases and 5536 deaths have been reported, with 16 498 new cases and 817 new deaths occurring in last 24 hours. Therefore, the world should work together to fight against this pandemic. Here, we review the recent advances in COVID-19, including the insights in the virus, the responses of the host cells, the cytokine release syndrome, and the therapeutic approaches to inhibit the virus and alleviate the cytokine storm. By sharing knowledge and deepening our understanding of the virus and the disease pathogenesis, we believe that the community can efficiently develop effective vaccines and drugs, and the mankind will eventually win this battle against this pandemic.
Betacoronavirus ; China ; epidemiology ; Coronavirus Infections ; epidemiology ; therapy ; Humans ; Pandemics ; Pneumonia, Viral ; epidemiology ; therapy

Humans ; COVID-19 ; China/epidemiology*