The functional division of arbuscular mycorrhizal fungi and earthworm to efficient cooperation on phytoremediation in molybdenum (Mo) contaminated soils.

Single phytoremediation has limited capacity to restore soil contaminated with extreme Mo due to its low metal accumulation. Soil organisms can help compensate for this deficiency in Mo-contaminated soils. However, there is limited information available on the integrated roles of different types of soil organisms, particularly the collaboration between soil microorganisms and soil animals, in phytoremediation. The objective of this study is to investigate the effects of a combination of arbuscular mycorrhizal fungi (AMF) and earthworms on the remediation of Mo-contaminated soils by alfalfa (Medicago sativa L.). The results indicated that in the soil-alfalfa system, earthworms effectively drive soil Mo activation, while AMF significantly improve the contribution of the translocation factor to total Mo removal (TMR) in alfalfas (p < 0.05). Meanwhile, compared to individual treatments, the combination of AMF and earthworm enhanced the expression of alfalfa root specific Mo transporter - MOT1 family genes to increase alfalfa uptake Mo (p < 0.05). This alleviated the competition between P/S nutrients and Mo on non-specific Mo transporters-P/S transporters (p < 0.05). Additionally, the proportion of organelle-bound Mo in the root was reduced to decrease Mo toxicity, while the cell wall-bound Mo proportion in the shoot was increased to securely accumulate Mo. The contributions of inoculants to alfalfa TMR followed the order (maximum increases): AMF + E combination (274.68 %) > alone treatments (130 %). Overall, the "functional division and cooperation" between earthworm and AMF are of great importance to the creation of efficient multi-biological systems in phytoremediation.

Effects of arbuscular mycorrhizal fungi on the growth and toxic element uptake of Phragmites australis (Cav.) Trin. ex Steud under zinc/cadmium stress.

Arbuscular mycorrhizal fungi (AMF) play an important role in improving plant tolerance and accumulation of zinc (Zn) and cadmium (Cd). The growth, physiology and absorption of elements and transport in Phragmites australis (P. australis) were investigated under Zn and Cd stress to identify the transport mechanisms of toxic trace elements (TE) under the influence of AMF. Thus, AMF were observed to alleviate the toxic effects of Zn and Cd on P. australis by increasing plant biomass and through different regulatory patterns under different TE concentrations. The activities of superoxide dismutase (SOD) and ascorbate peroxidase (APX) increased under Zn stress, and the activities of SOD, catalase (CAT), peroxidase (POD), and APX significantly increased under high concentrations of Cd. AMF differ in their strategies of regulating the transport of different metals under TE stress. Under Zn stress, the concentration of Zn in P. australis decreased by 10-57%, and the effect on Zn translocation factor (TFZn) was concentration-dependent. AMF increased the TFZn under low concentration stress, but decreased under high concentration stress. Under Cd stress, the concentration of Cd increased by as much as 17-40%, and the TFCd decreased. AMF were also found to change the interaction of Zn×Cd. In the absence of AMF, Cd exposure decreased the Zn concentrations in P. australis at Zn100 mg/L and Zn300 mg/L, while it increased the contents of Zn at Zn700 mg/L. The opposite trend was observed following treatment with AMF. However, regardless of the concentration of Cd, the addition of Zn decreased the concentration of Cd in both treatments in both the presence and absence of AMF. Under different TE stress conditions, the regulation of metal elements by AMF in host plants does not follow a single strategy but a trade-off between different trends of transportations. The findings of our study are important for applying AMF-P. australis systems in the phytoremediation of Zn-Cd co-contaminated ecosystems.

Alantolactone inhibits cell autophagy and promotes apoptosis via AP2M1 in acute lymphoblastic leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is an aggressive hematopoietic malignancy that is most commonly observed in children. Alantolactone (ALT) has been reported to exhibit anti-tumor activity in different types of cancer. The aim of the present study was to investigate the anti-tumor activity and molecular mechanism of ALT in ALL. METHODS: ALL cell lines were treated with 1, 5 and 10 µM ALT, and cell viability was assessed using an MTT assay and RNA sequencing. Flow cytometry, JC-1 staining and immunofluorescence staining assays were used to measure cell apoptosis and autophagy. Additionally, western blot analysis was used to detect expression of apoptosis and autophagy related proteins. Finally, the effects of ALT on tumor growth were assessed in a BV173 xenograft nude mouse model. RESULTS: ALT inhibited the proliferation of ALL cells in a dose-dependent manner. Additionally, it was demonstrated that ALT inhibited cell proliferation, colony formation, autophagy, induced apoptosis and reduced tumor growth in vivo through upregulating the expression of adaptor related protein complex 2 subunit mu 1 (AP2M1). Moreover, the autophagy activator rapamycin, attenuated the pro-apoptotic effects of ALT on BV173 and NALM6 cell lines. Overexpression of AP2M1 decreased the expression of Beclin1 and the LC3-II/LC3-1 ratio, and increased p62 expression. Knockdown of Beclin1 increased the levels of bax, cleaved caspase 3 and cytochrome C, and decreased bcl-2 expression. CONCLUSIONS: The present study demonstrated that ALT exerts anti-tumor activity through inducing apoptosis and inhibiting autophagy by upregulating AP2M1 in ALL, highlighting a potential therapeutic strategy for treatment of ALL.

Molybdenum-mediated nitrogen accumulation and assimilation in legumes stepwise boosted by the coexistence of arbuscular mycorrhizal fungi and earthworms.

Molybdenum (Mo) is a critical micronutrient for nitrogen (N) metabolism in legumes, yet the impact of Mo on legume N metabolism in the context of natural coexistence with soil microorganisms remains poorly understood. This study investigated the dose-dependent effect of Mo on soil N biogeochemical cycling, N accumulation, and assimilation in alfalfa under conditions simulating the coexistence of arbuscular mycorrhizal fungi (AMF) and earthworms. The findings indicated that Mo exerted a hormetic effect on alfalfa N accumulation, facilitating it at low concentrations (below 29.98 mg/kg) and inhibiting it at higher levels. This inhibition was attributed to Mo-induced constraints on C supply for nitrogen fixation. Concurrently, AMF colonization enhanced C assimilation in Mo-treated alfalfas by promoting nutrients uptake, particularly Mg, which is crucial for chlorophyll synthesis. This effect was further amplified by earthworms, which improved AMF colonization (p < 0.05). In the soil N cycle, these organisms exerted opposing effects: AMF enhanced soil nitrification and earthworms reduced soil nitrate (NO3--N) reduction to jointly increase soil phyto-available N content (p < 0.05). Their combined action improved alfalfa N assimilation by restoring the protein synthesis pathway that is compromised by high Mo concentrations, specifically the activity of glutamine synthetase. These findings underscored the potential for soil microorganisms to mitigate N metabolic stress in legumes exposed to elevated Mo levels.

The trade-off regulation of arbuscular mycorrhiza on alfalfa growth dose-dependent on gradient Mo exposure.

Molybdenum (Mo) is an essential nutrient for leguminous plants, but the effects of Mo exposure on plant growth, especially in relation to soil microorganisms, are not fully understood. This study employed alfalfa (Medicago sativa L.) to evaluate the physiochemical responses to gradient soil Mo variations and explore the potential regulatory role of rhizosphere microorganism - arbuscular mycorrhizal fungi (AMF) in modulating Mo's impact on plant physiology, with a focus on metabolic pathways. The results showed that Mo exerted hormetic effect (facilitation at low doses; inhibition at high doses) on alfalfa growth, promoting biomass (below 90.94 mg/kg, with a 63.98 % maximum increase), root length (below 657.11 mg/kg, with a 39.29 % maximum increase), and plant height (below 304.03 mg/kg, with an 18.4 % maximum increase). Excess Mo (1000 mg/kg) resulted in a reduction in photosynthesis and biomass growth due to increased oxidative stress (p < 0.05). Within the stimulatory zones, AMF enhanced Mo accumulation in alfalfa, augmenting its phytological effects. Exceed the stimulatory zones, AMF enhanced alfalfa Fe uptake and reduced the generation of reactive oxygen species (ROS) induced by excess Mo by shifting the redox homeostasis-controlled enzyme from peroxidase (POD) to superoxide dismutase (SOD), thereby improving alfalfa's tolerance to Mo. Metabolomic analysis further revealed that AMF promoted the biosynthesis of indole acetic acid (IAA) and various amino acids in Mo-stressed alfalfa (p < 0.05), which accelerated alfalfa growth and mitigated Mo-induced phytotoxicity. These insights provide a foundation for developing sustainable management strategies for Mo-exposed soils using AMF inoculants, such as minimizing Mo fertilizer application in Mo-deficient soils and facilitating the reclamation of Mo-contaminated soils.

Arsenic trioxide inhibits the Hedgehog pathway which is aberrantly activated in acute promyelocytic leukemia.

BACKGROUND/AIM: Dysregulated Hedgehog (Hh) signaling has been implicated in several human malignancies. Hh signaling inhibitors are predicted to have a minimal effect when the Smoothened receptor is mutated. Implications that Gli proteins are molecular targets of arsenic trioxide (ATO) action prompted us to investigate the expression of Hh signaling in acute promyelocytic leukemia (APL) and the influence of ATO on the Hh signaling pathway in APL. METHODS: Quantitative real-time reverse transcription polymerase chain reaction and Western blot were employed to analyze the expression of Hh pathway components and the influence of ATO on the Hh signaling pathway in APL. RESULTS: The expression of Hh pathway components was significantly upregulated in APL. In newly diagnosed APL patients, Gli2 expression was significantly positively correlated with Gli1 (R = 0.57, p < 0.001) and Smo (R = 0.56, p < 0.001) and the expression of Hh pathway components was significantly higher in the high WBC group (p < 0.05). ATO can significantly downregulate the expression of Hh pathway components in vitro and in vivo (p < 0.05). CONCLUSION: The Hh pathway is aberrantly activated in APL and associated with a bad prognostic factor. ATO can effectively inhibit the expression of the Hh pathway. The obtained data give the first clinical evidence for the application of ATO in tumors exhibiting an aberrantly activated Hh pathway.

Effects of Ag nanoparticles on plant growth, Ag bioaccumulation, and antioxidant enzyme activities in Phragmites australis as influenced by an arbuscular mycorrhizal fungus.

Ag nanoparticles (AgNPs) are considered an emerging contaminant in recent years, and their harmful effects on plants pose new concerns, especially in coexistence with soil microorganisms. Arbuscular mycorrhizal fungi (AMF), as mutualistic fungi with most terrestrial plants, may contribute to alleviating nanotoxicity in plants. Herein, AgNP toxicity of different concentrations (1, 5, 10, 50, 100 mg/kg) on reed (Phragmites australis (Cav.) Trin. ex Steudel) as influenced by mycorrhizal inoculation with Funneliformis mosseae was investigated. The results revealed that concentration is the main factor influencing the AgNP phytotoxicity; AgNP dose had biphasic effects on AMF colonization, plant biomass, and antioxidant enzyme activities. Thereinto, different antioxidant enzymes had different tolerances to AgNP stress, and the turning point of their activities was respectively the following: POD-5 mg/kg < SOD-10 mg/kg < CAT-50 mg/kg. The growth configuration (root:shoot ratio) of Phragmites australis increased firstly and then decreased to cope with the increasing AgNP concentration. Additionally, the Ag accumulation and translocation of AgNP-exposed plants were relatively lower than that of equivalent Ag+-exposed plants. However, AMF inoculation improved plant antioxidant capability and biomass growth in response to AgNP-induced toxicity. Meanwhile, AMF effectively regulated the root:shoot ratio to accommodate AgNP stress. The linear model fittings and heat maps showed that the mycorrhizal plants exhibited a higher Ag accumulative rate and root partitioning (Ag organ distribution: root > stem > leaf) than the non-inoculated plants. Overall, our results demonstrated that AMF could diminish the negative effects induced by AgNPs and promote Ag immobilization in plant roots so as to alleviate AgNP-posed environmental risks.

Differential interference of copper with endophytic bacterial inoculation: Atrazine decontamination in Acorus tatarinowii and culture solution.

To clarify the interference effects of inorganic ions, Acorus tatarinowii and endophytic bacterium Herbaspirillum huttiense (Hh) were combined to decontaminate atrazine pollution under different copper levels. This study verified inoculation effects and revealed the complicated processes of atrazine transformation in solutions. 35.9% leaf biomass was promoted by Hh inoculation, and the value was lowered to 7.87% by high doses of copper. The changing trend of leaf N, K, and S contents, and tiller numbers were consistent with that of leaf biomass. Hh injection improved atrazine accumulation by 43.5% in roots, and under copper interference, this value lowered to 10.6%. Hh promoted atrazine deethylation in plants, which was copper-dose dependent in different plant organs. In solutions, atrazine was conjugated with small-molecule secretions at m/z 118, detoxicated into 2-hxydroatrazine and 2-hydroxy-4-acetamido-atrazine, then the triazine ring opened. Copper interference had a more significant impact on residual atrazine conversion products than Hh inoculation treatments. Hh treatment promoted the ring-opening degradation of atrazine in water. The addition of high doses of copper ions promoted the oxidative process of atrazine while inhibiting its ring-opening transformation process in water.

How a functional soil animal-earthworm affect arbuscular mycorrhizae-assisted phytoremediation in metals contaminated soil?

Phytoremediation is a promising and sustainable technology to remediate the risk of heavy metals (HMs) contaminated soils, however, this way is limited to some factors contributing to slow plant growth and low remediation efficiency. As soil beneficial microbe, arbuscular mycorrhizal fungi (AMF) assisted phytoremediation is an environment-friendly and high-efficiency bioremediation technology. However, AMF-symbiotic formation and their functional expression responsible for HMs-polluted remediation are significantly influenced by edaphic fauna. Earthworms as common soil fauna, may have various effects on formation of AMF symbiosis, and exhibit synergy with AMF for the combined remediation of HMs-contaminated soils. For now, AMF-assisted phytoremediation incorporating earthworm coexistence is scarcely reported. Therefore, the main focus of this review is to discuss the AMF effects under earthworm coexistence. Effects of AMF-symbiotic formation influenced by earthworms are fully reviewed. Moreover, underlying mechanisms and synergy of the two in HMs remediation, soil improvement, and plant growth were comprehensively elucidated. Phenomenon of "functional synergism" between earthworms and AMF may be a significant mechanism for HMs phytoremediation. Finally, this review analyses shortcomings and prescriptions in the practical application of the technology and provides new insights into AMF- earthworms synergistic remediation of HMs-contaminated soils.

Recent advances in responses of arbuscular mycorrhizal fungi - Plant symbiosis to engineered nanoparticles.

The application of engineered nanomaterials (ENMs) is increasing in all walks of life, inevitably resulting in a high risk of ENMs entering the natural environment. Recent studies have demonstrated that phytoaccumulation of ENMs in the environment may be detrimental to plants to varying degrees. However, plants primarily assimilate ENMs through the roots, which are inevitably affected by rhizomicroorganisms. In this review, we focus on a group of common rhizomicroorganisms-arbuscular mycorrhizal fungi (AMF). These fungi contribute to ENMs immobilization and inhibition of phytoaccumulation, improvement of host plant growth and activation of systematic protection in response to excess ENMs stress. In present review, we summarize the biological responses of plants to ENMs and the modulatory mechanisms of AMF on the immobilization of ENMs in substrate-plant interfaces, and indirectly regulatory mechanisms of AMF on the deleterious effects of ENMs on host plants. In addition, the information of feedback of ENMs on mycorrhizal symbiosis and the prospects of future research on the fate and mechanism of phyto-toxicity of ENMs mediated by AMF in the environment are also addressed. In view of above, synergistic reaction of plants and AMF may prove to be a cost-effective and eco-friendly technology to bio-control potential ENMs contamination on a sustainable basis.

Umbilical Cord Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Deliver miR-21 to Promote Corneal Epithelial Wound Healing through PTEN/PI3K/Akt Pathway.

Objective: Rapid restoration of corneal epithelium integrity after injury is particularly important for preserving corneal transparency and vision. Mesenchymal stem cells (MSCs) can be taken into account as the promising regenerative therapeutics for improvement of wound healing processes based on the variety of the effective components. The extracellular vesicles form MSCs, especially exosomes, have been considered as important paracrine mediators though transferring microRNAs into recipient cell. This study investigated the mechanism of human umbilical cord MSC-derived small extracellular vesicles (HUMSC-sEVs) on corneal epithelial wound healing. Methods: HUMSC-sEVs were identified by transmission electron microscopy, nanoparticle tracking analysis, and Western blot. Corneal fluorescein staining and histological staining were evaluated in a corneal mechanical wound model. Changes in HCEC proliferation after HUMSC-sEVs or miR-21 mimic treatment were evaluated by CCK-8 and EdU assays, while migration was assessed by in vitro scratch wound assay. Full-length transcriptome sequencing was performed to identify the differentially expressed genes associated with HUMSC-sEVs treatment, followed by validation via real-time PCR and Western blot. Results: The sEVs derived from HUMSCs can significantly promote corneal epithelial cell proliferation, migration in vitro, and corneal epithelial wound healing in vivo. Similar effects were obtained after miR-21 transfection, while the beneficial effects of HUMSC-sEVs were partially negated by miR-21 knockdown. Results also show that the benefits are associated with decreased PTEN level and activated the PI3K/Akt signaling pathway in HCECs. Conclusion: HUMSC-sEVs could enhance the recovery of corneal epithelial wounds though restraining PTEN by transferring miR-21 and may represent a promising novel therapeutic agent for corneal wound repair.

Earthworm and arbuscular mycorrhiza interactions: Strategies to motivate antioxidant responses and improve soil functionality.

Earthworms and arbuscular mycorrhizal fungi (AMF) act synergistically in the rhizosphere and may increase host plant tolerance to Cd. However, mechanisms by which earthworm-AMF-plant partnerships counteract Cd phytotoxicity are unknown. Thus, we evaluated individual and interactive effects of these soil organisms on photosynthesis, antioxidant capacity, and essential nutrient uptake by Solanum nigrum, as well as on soil quality following Cd exposure (0-120 mg kg-1). Decreases in biomass and photosynthetic activity, as well as nutrient imbalances were observed in Cd-stressed plants; however, the addition of AMF and earthworms reversed these effects. Cd exposure increased superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities, whereas inoculation with Rhizophagus intraradices decreased those. Soil enzymatic activity decreased by 15-60% with increasing Cd concentrations. However, Cd-mediated toxicity was partially reversed by soil organisms. Earthworms and AMF ameliorated soil quality based on soil enzyme activity. At 120 mg kg-1 Cd, the urease, catalase, and acid phosphatase activities were 1.6-, 1.4-, and 1.2-fold higher, respectively, in soils co-incubated with earthworms and AMF than in uninoculated soil. Cd inhibited shoot Fe and Ca phytoaccumulation, whereas AMF and earthworms normalized the status of essential elements in plants. Cd detoxification by earthworm-AMF-S. nigrum symbiosis was manifested by increases in plant biomass accumulation (22-117%), chlorophyll content (17-63%), antioxidant levels (SOD 10-18%, POD 9-25%, total polyphenols 17-22%, flavonoids 15-29%, and glutathione 7-61%). It also ameliorated the photosynthetic capacity, and macro- and micronutrient statuses of plants; markedly reduced the levels of malondialdehyde (20-27%), superoxide anion (29-36%), and hydrogen peroxide (19-30%); and upregulated the transcription level of FeSOD. Thus, the combined action of earthworms and AMF feasibly enhances metal tolerance of hyperaccumulating plants and improves the quality of polluted soil.

Integration of earthworms and arbuscular mycorrhizal fungi into phytoremediation of cadmium-contaminated soil by Solanum nigrum L.

Arbuscular mycorrhizal fungi (AMF) and earthworms independently enhance plant growth, heavy metal (HM) tolerance, and HM uptake, thus they are potential key factors in phytoremediation. However, few studies have investigated their interactions in HM phytoextraction by hyperaccumulators. This study highlights the independent and interactive effects of earthworms and AMF on Solanum nigrum. Plants inoculated with either AMF or earthworms exhibited ameliorated growth via enhancement of productivity, metal tolerance, and phosphorus (P) acquisition. Co-inoculation with both had more pronounced effects on plant biomass and P acquisition in shoots, but not in roots, and in Cd-polluted soils it significantly promoted (P < 0.05) shoot biomass (20.7-134.6 %) and P content (20.4-112.0 %). AMF and earthworms increased Cd accumulation in plant tissues, but only AMF affected Cd partitioning between shoots and roots. Although AMF decreased root-to-shoot translocation of Cd at high Cd levels, this was counterbalanced by earthworms. Both AMF and its combination with earthworms enhanced Cd phytoavailability by altering Cd chemical fractions and decreasing pH. Co-inoculation increased Cd removal amounts up to 149.3 % in 120 mg kg-1 Cd-spiked soils. Interactions between the two organisms were synergistic in Cd phytoextraction. Thus, earthworm-AMF-plant symbiosis potentially plays an essential role in phytoremediation of HM-polluted soils.

Construction of CII-Specific CAR-T to Explore the Cytokine Cascades Between Cartilage-Reactive T Cells and Chondrocytes.

Cytokine cascades exist in many autoimmune disorders which amplify and sustain the autoimmune process and lead to chronic inflammatory injury to the host tissues. Increasing evidence indicates that chondrocytes can interact with T cells, which may be a crucial event in inflammatory arthritis. To address the reciprocal influences of cartilage-reactive T cells and chondrocytes, we constructed cartilage-reactive T cells by developing a type II collagen-specific chimeric antigen receptor (CII-CAR). An in vitro co-culture model of CII-CAR-T cells and fresh cartilage was developed, in which CII-CAR-T displayed specific proliferative capacity and cytokine release against fresh cartilage samples, and chondrocytes could respond to CII-CAR-T cells by secreting IL-6. The proposed model will help us to explore the possible cytokine cascades between cartilage-reactive T cells and cartilage.

[Effect of Daunorubicin on Release and Procoagulant Activity of Microparticles Derived from Acute Promyelocytic Leukemia Cells].

OBJECTIVE: To investigate the effect of daunorubicin on the number and procoagulant activity of Microparticles derived from acute promyelocytic leukemia(APL) cells. METHODS: APL cells were isolated from bone Marrow of 5 newly diagnosed APL patients, the bone marrow mononuclear cells were collected from 5 patients with iron deficiency anemia as control.APL cells were treated with different concentration of daunorubicin(0.1,0.5,1.0 and 2.0µmol/L) for 24 h. Microparticles were extracted from the cell culture medium for qualitative anaysis of the extracted microparticles.The morphologic features of the microparticles were observed by transmission electron microscopy.The number of microparticles was detected by flow cytometry.The procoagulant activity of microparticles was measured by recalcification time assays. RESULTS: Under a transmission electron microscope, theextracted microparticles took a round or oval morphology with a transparent center,and their diameters were arund 100nm, consistent with the morphological characteristics of microparticles. Compared with bone marrow mononuclear cells-derived microparticles,the counts of the bone marrow APL cells-derived microparticles significantly increased(P<0.05).Daunorubicin increased the shedding of microparticles in a dose-dependent manner(r=0.73,P<0.01).Compared with normal bone marrow mononuclear cells-derived microparticles,bone marrow APL cells-derived microparticles showed higher procoagulant activity(P<0.05).Daunorubicin treatment enhanced the prccoagulant activity of APL cells-derived microparticles which paralleled the increasing drug concentrations(r=-0.78,P<0.01). CONCLUSION: Daunorubicin can promote the release of APL cells-derived microparticles and enhance their related procoagulan activity.

Stratification of gene coexpression patterns and GO function mining for a RNA-Seq data series.

RNA-Seq is emerging as an increasingly important tool in biological research, and it provides the most direct evidence of the relationship between the physiological state and molecular changes in cells. A large amount of RNA-Seq data across diverse experimental conditions have been generated and deposited in public databases. However, most developed approaches for coexpression analyses focus on the coexpression pattern mining of the transcriptome, thereby ignoring the magnitude of gene differences in one pattern. Furthermore, the functional relationships of genes in one pattern, and notably among patterns, were not always recognized. In this study, we developed an integrated strategy to identify differential coexpression patterns of genes and probed the functional mechanisms of the modules. Two real datasets were used to validate the method and allow comparisons with other methods. One of the datasets was selected to illustrate the flow of a typical analysis. In summary, we present an approach to robustly detect coexpression patterns in transcriptomes and to stratify patterns according to their relative differences. Furthermore, a global relationship between patterns and biological functions was constructed. In addition, a freely accessible web toolkit "coexpression pattern mining and GO functional analysis" (COGO) was developed.

[Experimental advance of targeted medicines for chronic myeloid leukemia--review].

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder from hematopoietic stem cell disorder characterized by the consecutive expression of bcr-abl gene, and the translation product of which has enhanced tyrosine kinase activity and can activate a series of downstream signal transduction proteins and results in the occurence of CML. Although the application of imatinib (IM) makes nearly all patients with CML in chronic phase achieve a complete hematologic remission, and 90%of those treated in the early chronic phase achieve a complete cytogenetic remission, but the development of resistance to IM in the course of treatment and even in the beginning of the treatment forced people to develop new agents and to combine the new agents with IM in order to achieve better therapeutic result. This article reviews the experimental advances of targeted therapeutics in CML recent years.