Oliver Ottmann

..Continued detection of bcr-abl transcripts after 2 to 3 months on imatinib identifies patients who will ultimately experience relapse and in whom additional or alternative antileukemic treatment should be initiated...

..This warrants the application of HDI-based therapies in poor-risk Ph+ ALL, and the use of Akt/mTor inhibitors to overcome HDI resistance in AML...

..To examine whether GliPR plays a role as HIV dependency factor (HDF), we tested the effect of GliPR suppression by siRNA on HIV-1 replication...

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..As the remaining open questions are resolved, clinical benefits may be achieved consistently and with a favorable cost benefit ratio...

..Further studies are warranted to test the effects of imatinib in combination with other agents and to define the mechanisms of resistance to imatinib...

..Imatinib in combination with intensive chemotherapy has yielded promising results as front-line therapy, but its value as monotherapy in newly diagnosed Ph+ALL is not known...

..Better understanding of targeted therapies, including strategies based on recruitment of host immune functions, as well as the prudent use of active chemotherapy agents, may eventually improve the outlook for patients with Ph(+) ALL...

..Dasatinib represents a safe and effective treatment option and an important therapeutic advance for patients with Ph-positive ALL. This trial was registered at www.clinicaltrials.gov as #CA180015...

..Selection of those patients likely to benefit from growth factors in a specific clinical setting is a worthwhile endeavour...

..Following SCT, the pre-emptive use of imatinib appears to reduce the relapse rate. Novel immunotherapeutic interventions and combinations of TKI are also being explored...

..Glivec can already be considered an important element in the treatment of Ph+ ALL, although the most effective ways of employing this novel agent remain to be established...

..SNPs of PDGFR genes do not appear to play a role in patient's susceptibility to clinically severe edema formation during treatment with STI571...

..Expression of the MEBE genes is regulated by FLI1 and c-MYC, which are potential upstream targets of the MEBE signature...

..To study the incidence and prognostic impact of mutations in Additional sex comb-like 1 (ASXL1) in a large cohort of patients with myelodysplastic syndrome (MDS)...

..In summary, these data suggest a crucial role of factors able to upregulate PML for As2O2-induced cell death...

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..However, little is known about the incidence and prognostic impact of IDH1 and IDH2 mutations in myelodysplastic syndromes...

..Both schedules of imatinib have acceptable toxicity and facilitate SCT in CR1 in the majority of patients, but concurrent administration of imatinib and chemotherapy has greater antileukemic efficacy...

..This provides a rationale for the frontline use of kinase inhibitors active against these BCR-ABL mutants...

..83; 95% confidence interval, 1.31-6.12; P = .008). These results show a negative prognostic impact of SRSF2 mutations in MDS. SRSF2 mutations may become useful for clinical risk stratification and treatment decisions in the future...

..Here, we investigated the biological effect of the new specific dual Src/Abl kinase inhibitor AZD0530 on Ph+ leukaemic cells...

..Furthermore, the cells displayed a del(9)(p21.1 approximately p23), typically associated with loss of CDKN2A and CDKN2B. The ALL-VG cell line may serve as a tool for the study of ETV6/ABL1...

..Glu255Lys is within the motif important for forming the pocket of the ATP-binding site in ABL and it is highly conserved across species. In conclusion, Ph(+) ALL samples resistant to STI571 have a unique mutation Glu255Lys of BCR-ABL...

..We conclude that the presence of macrophages or IL-18R+ T cells that can respond directly to IL-18 is essential for the proinflammatory effects of IL-18 in synovitis in RA...

..Although the efficacy of leukapheresis in terms of prompt cytoreduction is generally accepted, published data regarding the clinical value of immediate therapeutic leukapheresis are limited and conflicting...

..Our data suggest a differential effect of VPA on the small population of AML progenitor cells and the bulk of aberrantly differentiated blasts in the majority of AML samples tested...

..However, resistance to this drug develops within a few months in most patients. We aimed to predict resistance to STI571...

..Here we investigated whether a folate excess impairs monocyte differentiation, a putative anti-inflammatory action of low-dose MTX...

..The data show that Bcr-Abl levels in PB and BM after 2 weeks of imatinib treatment and in BM after 4 weeks have predictive relevance and may guide the application of additional therapies...

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..The findings suggest that the mutation exists in a very small subpopulation of leukemic cells at the beginning of STI571 therapy...

..This may result in the proliferation of Ph + leukemic cells even in the presence of STI571...

..The optimal type of CNS-directed treatment and the extent of protection afforded by prophylactic cranial irradiation remain to be defined...

..INTERPRETATION AND CONCLUSIONS: Our study establishes that LAQ824 is a promising agent for the therapy of acute lymphoblastic leukemia...

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..The expression of selected genes was confirmed by real-time polymerase chain reaction. Our data encompass the first extensive transcriptional profile of human hematopoiesis during in vitro lineage-specific differentiation...

..We assessed the prognostic impact of a known single nucleotide polymorphism (SNP) located in the mutational hotspot of WT1 in patients with cytogenetically normal acute myeloid leukemia (CN-AML) in the context of other prognostic markers...

..Thus, immunostrategies designed to enhance ALL sensitivity toward NK cell-mediated cytotoxicity should focus on mechanisms of NK cell activation...

..It is suggested, therefore, that this technique be an alternative method to monitor HIV-1 replication in vitro...

..Conversely, patients with clinically or cytogenetically defined poor-risk features are candidates for trials of upfront imatinib in combination with other agents...

..In conclusion, nilotinib is an effective and well-tolerated treatment in imatinib-resistant and -intolerant CML-AP. This trial is registered at www.clinicaltrials.gov as NCT00384228...

..Orally administered imatinib is an effective and well-tolerated treatment for patients with CML in accelerated phase. A daily dose of 600 mg is more effective than 400 mg, with similar toxicity...

..These findings indicate that ZOL is a potent antileukemic agent that augments synergistically the anti-Ph+ leukemia activity of imatinib mesylate...

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..The results demonstrate the applicability of genetic proliferation control to coordinate growth of different cell types in cocultures...

..These findings suggest that the combination of ZOL and imatinib accelerate the eradication of Ph+ clone, resulting in better prognosis of Ph+ leukaemia patients who have not yet acquired mutations...

..CONCLUSIONS: Treatment with VPA/ATRA results in transient disease control in a subset of patients with AML that has evolved from a myeloproliferative disorder but not in patients with a primary or MDS-related AML...

..Preclinical in vitro studies have shown that nilotinib (AMN107), a new BCR-ABL tyrosine kinase inhibitor, is more potent than imatinib against CML cells by a factor of 20 to 50...

..In conclusion, decitabine synergizes with Vitamin D3 to induce CD11b and CD14 expression, likely by enhancing PU.1/c-jun and Sp1 transcriptional activity...

..Our results indicate that selective interference with the oligomerization domain of ETO could provide a promising strategy to inhibit the oncogenic properties of the leukemia-associated fusion protein RUNX1/ETO...

..Imatinib has demonstrated synergistic effects in vitro with mitoxantrone, etoposide, and cytarabine...

..Furthermore, one day of ZOL pretreatment augmented the sensitivity of imatinib and Ara-C. Therefore, concurrent or sequential administration of ZOL with imatinib, HU, Ara-C, or DNR may increase the efficacy of leukemia treatment...

..Additional clinical studies are warranted to explore the efficacy and feasibility of imatinib used in combination with other antileukemic drugs...

..These results demonstrate that Bim and Bad account for most, perhaps all, imatinib-induced killing of Bcr/Abl+ leukemic cells and suggest previously undescribed drug combination strategies for cancer therapy...

..Monitoring the actual BCR-ABL inhibition in nilotinib treated patients using pCRKL as a surrogate is a means to establish effective dosing and to characterize resistance mechanisms against nilotinib...

..ZOL also affected the coordinate expression patterns of several cell cycle regulators during the execution of anti-tumor activity...

..5 mL samples tested positive. For higher dilutions, a PB volume of 5 or 10 ml was required to improve sensitivity. The study showed the feasibility of RQ-PCR standardization independent of the PCR machine used...

..In summary, monotherapy with SU11248 induced partial remissions of short duration in acute myeloid leukemia (AML) patients. Further evaluation of this compound, for example in combination with chemotherapy, is warranted...