T Naoe

..Comprehensive genome research will deepen the understanding of AML to promote the development of new classification and treatment. This review focuses on gene mutations that were recently discovered by genome sequencing...

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..Exploring the mechanism by which FLT3 mutations cause autoactivation and uncontrolled signaling might lead to a better understanding of how FLT3 becomes oncogenic and provide insights for the development of new drugs...

..This review focuses on the clinical significance of the NPM1 gene in hematological malignancies and newly discovered roles of NPM associated with oncogenesis...

..Studies on leukemia relapse have thus served as a model of clonal progression, which can be serially observed, including selection by chemotherapy, induction of resistant phenotype, and genetic alteration...

..Challenging studies with TKIs have also been reported for acute myeloid leukemia. This review will focus on recent trials of TKIs against oncogenic tyrosine kinases (ABL, PDGFRs, FLT3 and KIT) in myeloid malignancies...

..Another HSP90 inhibitor, radicicol, also induced apoptosis selectively in transformed 32D cells. HSP90 is a promising target for the treatment of AML with mutant FLT3...

..Basic and clinical research into ATRA-resistance provides new directions for acute myeloid leukemia therapy. Anti-leukemia therapy will continue to lead the field of chemotherapy in the coming decades...

..In summary, addition of HDCA is not beneficial for high-risk patients, and is not recommended for standard-risk patients receiving unrelated transplantation...

..These findings imply that targeting of Hsp90 will facilitate the development of anti-TDFLT3 therapy, and that Hsp90 is closely involved in the oncogenic activation of FLT3...

..These results demonstrate that Lyn is an important component of the signal transduction pathway specific to FLT3/ITD and can be a therapeutic target in the treatment of AML with FLT3/ITD...

..These findings suggest that FK228 is a promising agent to enhance ATRA-sensitivity in the treatment of APL...

..These results suggest that a GSTM1-null genotype in recipients protects against TRM after allogeneic HSCT. Further studies are needed to elucidate a mechanism of increased risk for TRM in GSTM1-positive recipients...

..These results demonstrate that the FLT3 gene is the target most frequently mutated to become constitutively active in AML...

..These data suggest that TEL-Syk fusion protein in the cytoplasm leads to the constitutive activation of PI3-K/Akt, MAPK and STAT5 signal pathways, which are closely involved in IL-3-independent cell proliferation of BaF3 cells...

..073; within 120 days, P = 0.028), whereas CR rates and relapse frequencies were similar. The null genotype of GSTT1 might be associated with increased toxicity after chemotherapy...

..Thus, patients who developed extensive chronic GVHD had better survivals (P = 0.0217), and those who developed grade III-IV acute GVHD had worse survivals (P = 0.0023) than did the others...

..Our patients could not be accurately classified when the proposed prognostic models from Western countries were used, thus indicating the need for a different model to identify high-risk patients...

..As the presence of the C-A-A haplotype reduced relapse risk and improved survival after allogeneic HSCT, this CTLA-4 haplotype may provide useful information for donor selection...

..These findings suggest that xenotransplantation into immunodeficient mice provides a useful model to study the leukemia niche...

..This novel agent might be useful in the treatment of lymphoid malignancies, because the above concentrations are clinically achievable in vivo according to a recent clinical study...

..Avoiding intensified immunosuppression that damages vascular endothelium until the resolution of i-TAM may improve transplant outcome...

..Thus we examined that modified continual reassessment method (mCRM) is applicable for deciding appropriate conditioning of allogeneic BM transplantation...

..We investigated the mechanism responsible for imatinib (IM) resistance in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) cell lines...

..In conclusion, more active homing of CCR9-926AG T cells to Peyer's patches may produce changes in Ag presentation and result in increased incidence of skin GVHD...

..Although it should be borne in mind that this meta-analysis was based on data abstracted from observational studies, these results may justify the risk-adapted therapeutic strategies for AML according to the FLT3 status...

..8%. Our data suggest that early detection of secondary cancers is very important in prolonging overall survival...

..Similar findings were observed in BCR/ABL-transfected Ba/F3. Our results elucidate the regulatory mechanism by which JAK2V617F modulates Skp2 gene expression through the STAT transcription factors...

..Protein instability of L1503R may be responsible for its intracellular retention and perhaps the larger VWF multimers, containing more mutant VWF subunits, are likely to be mal-processed and retained within the cell...

..To elucidate the molecular consequences of hereditary protein S (PS) deficiency, we investigated the in vitro synthesis of the PS missense mutants in COS-1 cells and their activated protein C (APC) cofactor activities...

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..e. high GTP-Rac) contributes to chemotherapy resistance in leukaemia cells. Our result suggests that inhibition of Rac and its signalling components might provide a useful anti-leukaemic strategy...

..62, 95% CI: 1.23-2.14, P=0.0007 for OS). This superiority of FK506 was not observed in SIB-HSCT cases. These findings indicate that the use of FK506 instead of CSP for GVHD prophylaxis is beneficial for patients undergoing UD-HSCT...

..This crossing-over was absent in the other twin, consistent with their fraternal state. Differently skewed X inactivation in the fraternal female twins might cause moderately severe and mild haemophilia B phenotypes, respectively...

..This finding may provide a basis to select a subgroup other than acute promyelocytic leukemia, which can benefit from As(2)O(3) treatment...

..These observations support the suggestion that control of the HDAC5 nucleocytoplasmic distribution might be associated with MEL cell differentiation, possibly through regulated GATA-1 transactivation...

..This is especially useful because it provides the patients with a better chance to receive an allogeneic HSC transplant...

..These results indicated that a subgroup of M0 patients has a high expression level of polycomb group gene BMI-1, which may contribute to leukemogenesis...

..Thus, the enzyme function of UGT2B17 in donor cells may affect the outcome of allogeneic HSCT...

..These results provide evidence to show that the N-CoR/HDAC3 co-repressor complex is involved in the aberrant transcription regulation in PML-RARalpha-expressing cells...

..027), and increase the risk of treatment failure by 2.8-fold...

..047). These results suggest that chronic GVHD following CBT is mild and has a graft-versus-malignancy effect...

..The unexpectedly high prevalence and the characteristics of SFPR may provide additional information on management following autologous SCT for acute myeloid leukemia...

..These results suggested that FHIT methylation was accumulated through the disease progression of MDS and AML, and the role of the FHIT gene as a tumor suppressor seemed different in AML and MDS...

..These findings suggested that the activation of adhesion molecules for leukocytes and expression of CXC chemokines in the lung are closely involved in triggering RAS...

..265). Imatinib-based therapy is a potentially useful strategy for newly diagnosed patients with Ph+ALL, not only providing them more chance to receive allo-HSCT, but also improving the outcome of allo-HSCT...

..These data suggest the possible involvement of this fusion protein in the leukemogenesis of B-ALL in a dual dominant-negative manner and the possibility that ALL with PAX5-PML can be treated with ATO...

..These results suggest that recruitment of the Sin3A-HDAC1 complex is related to downregulation of CD20 expression in CD20-negative B-cells after treatment with rituximab...

..In conclusion, it is necessary to introduce the first line therapy excluding the chemotherapy that can prolong survival in patients with high-risk MDS and MDS-AML...

..These results indicated that FLT3 overexpression may distinguish a novel disease entity in AML without FLT3 mutations and serve as a therapeutic target for FLT3 inhibitors...

..These results provide further evidence supporting causal relationships between inflammation and tumor growth, and demonstrate that bortezomib can target the tumor microenvironment...

..0303, respectively). These findings indicate that allogeneic c-HSCT should be offered to patients over 50 years only if the increased risk of TRM is acceptable, and that a non-TBI regimen is preferable when the transplant is performed...

..These results indicated that immature features of pre-B cells from CB, such as lack of TdT expression, and a short N region and few productive rearrangements in the IgH gene, might cause the delay in mature B-cell production...

..Finally, we found constitutive activation of MAP kinase and STAT5 in all clinical samples of AML patients with mutant Flt3. Our study shows the significance of internal tandem duplication of Flt3 receptors for leukemia cell expansion...

..These findings provide an insight on the mechanism of inducible mRNA expression of the KLF13 gene in erythroid cells...

..However, because one-third of treated patients fail to respond, the present study was an exploration of the characteristics of responders and non-responders to this treatment regimen...

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..09; P = .0258). Lack of MGMT protein expression is associated with aberrant promoter DNA methylation and appears to be a useful marker for predicting the survival of DLBCL patients...

..Taken together, these results suggest that GATA-1 and/or GATA-2 binding to a GATA site of the 3' enhancer of WT1 played an important role in WT1 gene expression...

..Cotreatment with ATO and the agent, which can induce sustained activation of JNK, might improve the outcome in MM therapy...

..These results suggest that TRL-01 is a useful cell line for studying not only the leukemia-related biology of MLL-ENL but also the intercellular association between leukemia and stroma...

..These results suggest that greater immunosuppression by methotrexate due to low MTHFR enzyme activity decreases the risk of acute GVHD in recipients of allogeneic HSCT...

..These results collectively suggest that TP53 mutation might be a functionally distinguishable class of mutation...

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..100%, P = 0.0001). Combinations of cytogenetics and ISS could readily predict prognosis. Quality of response is a poor surrogate marker for ultimate outcome. High-risk patients may need more effective treatment...

..Optimal pre-emptive strategy needs to be determined...

..As the complete nucleotide sequences of the human Ig heavy and Ig light V region loci have now been determined, the study of Ig genetics has entered into the super-information era...

..Taken together, it seems to suggest that each gene mutation could be separately responsible for severe FV deficiency, while this phenotype is due to the in-trans combination of the two defects...

..These data demonstrate that FLT3 activation induces beta-catenin tyrosine phosphorylation and nuclear localization, and thus suggest a mechanism for the association of FLT3 activation and beta-catenin oncogeneic signaling in AML...

..Peripheral blood stem cells might have an advantage in that they are associated with a low incidence of DCL development because PBSCT recipients receive a higher total cell dose than recipients of bone marrow or cord blood cells...

..A prospective intervention study is required to establish PK-based management in CML patients treated with imatinib...

..A multitude of novel agents have been developed and shown efficacy in overcoming imatinib resistance...

..These findings suggest that in situ detection of nuclear NPBC by immunohistochemistry could provide new insights into the pathogenesis and prognosis of AML and MDS...

..This Review describes the cutting edge of research on IVLBCL, and discusses the unsolved issues from biological and clinical perspectives to provide a better understanding of this rare lymphoma...

..She has remained in complete remission for over 3 years after diagnosis. This report suggests that rituximab-containing regimens could be safe and effective for elderly patients with IVL...

..The poor prognosis of CD7(+) CD56(+) M1-M7 suggests that this phenotype may act as a prognostic factor for AML, but this should be confirmed in further studies...

..Our results implicate that the sorted and purified stem cells are useful for more sensitive quantification of BCR-ABL-positive minimal residual disease...

..It was concluded that abnormal cytoplasmic localisation and/or significant reduction of NPM1 protein level rarely occurs in MDS. The increase in the number of nuclear NPM1-positive cells may be related to the progression of MDS...

..Our work provides new insights into PML regulation by post-translational modification and new information about the therapeutic mechanism of HDAC inhibitors...

..To evaluate the safety and efficacy of rituximab-containing chemotherapies for intravascular large B-cell lymphoma (IVLBCL)...

..These findings suggest that some epigenetic mechanisms may be partly related to the down-regulation of CD20 expression after rituximab treatment...

..These results suggest false-negative results for some types of organ involvement. Careful interpretation of the results of FDG-PET in IVLBCL is thus required...

..These results suggest that the monitoring of gene mutations in HSC and progenitors at diagnosis might be helpful for the early detection of TKI-resistant CML patients and facilitate appropriate therapeutic decision...

..Although these findings need to be confirmed with a larger number of patients, our data indicate that the MRD level at a given time during the early course in CR does not predict the outcome in Japanese patients...

..Thus, RRBL1 may be useful not only for analyses of mechanisms for the absence of CD20 expression in vitro but also for exploration of therapies against CD20- B-cell malignancies in vivo...

..Such observation may parallel the diverse expression of Alport's manifestations of human individuals with MYH9 disorders and suggest the limited requirement of the gene for maintenance and function of specific organs...

..Because the karyotype identified at diagnosis is the most relevant prognostic factor for AML, it should be possible to assess the efficacy more accurately on the basis of cytogenetic risk...

..It is also important to evaluate endothelial progenitor cell (EPC) contents in different stem cell sources to choose the best material for therapeutic angiogenesis...

..Although there are two major scoring systems for the clinical diagnosis of disseminated intravascular coagulation (DIC), the validity of these systems for leukemia-associated DIC remains to be confirmed...

..Concomitant hemorrhagic and thrombotic manifestations of cPAN are hardly treatable in patients with coagulation disorders, and the current case may represent a rare transfusion-related complication in hemophilia patients...

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..Therefore, optimal postremission therapy is a matter of vital concern. In particular, the clinical efficacy of allogeneic hematopoietic stem cell transplantation (HSCT) should be clarified...

..Our findings suggest that the WHO classification may be strengthened by greater emphasis on genetic/cytogenetic information...

..These results suggest that the NPM1 mutation is not necessarily an early event during leukemogenesis or that leukemia clones with NPM1 mutations are sensitive to chemotherapy...

..08; 95% CI, 1.11-3.90, P = 0.023). Further examination with a sufficiently larger population and other ethnicities are required to confirm our findings...

..88, and P = .31, respectively). MGMT promoter hypermethylation and p53 mutation are useful prognostic markers in DLBCL. The impact of MGMT inactivation on p53 mutation in DLBCL is unclear...

..These findings suggest that the antiapoptotic pathways from FLT3/ITD are more divergent than those from WtFLT3 and may represent targets for drug discovery with the potential of inducing selective cell death of human leukemia cells...

..The aim of this study was to evaluate the antileukemia activity of a novel FLT3 kinase inhibitor, FI-700...

..These findings indicate that the FLT3 JM domain plays an important role in receptor activation, and that the length-mutated JM domain induces ligand-independent receptor activation but also activates Wt-FLT3 in a trans-manner...

..In this review, we summarize the clinical and biological significance of FLT3-mutations and discuss the possibility of targeting FLT3 kinase for the treatment of leukemia...