S Meshinchi

..002). Multivariate analysis demonstrated that presence of the Flt3/ITD was the single most significant, independent prognostic factor for poor outcome (P =.009) in pediatric AML...

..FLT3 inhibitors are under evaluation for their efficacy in AML patients with FLT3 mutations...

..035), while the presence of more than 1 ITD was not clinically significant. Physical characteristics including the length of FLT3/ITD may influence FLT3 activation state by altering its structure and may impact response to therapy...

..Because a higher tumor burden at the time of second HSCT was associated with a higher risk of subsequent relapse, patients might benefit from reinduction therapy before the second HSCT...

..38). Activating mutations in the RTK/ras signaling pathway are common in pediatric AML, and their presence may identify a population at higher risk of poor outcome who may benefit from allogeneic BM transplantation...

..001) or with FLT3/WT (55%, P < .001). ITD-AR defines the prognostic significance in FLT3/ITD-positive AML, and ITD-AR greater than 0.4 is a significant and independent prognostic factor for relapse in pediatric AML...

..We compared multidimensional flow cytometry (MDF) with morphology in evaluating early marrow response to induction chemotherapy in pediatric ALL...

..The clinical trials are registered at www.clinicaltrials.gov as #NCT00002798 and #NCT00070174...

..01). AF1q expression may correlate with clinical outcome in pediatric AML, although it is not clear if AF1q is simply a marker of a more primitive phenotype or contributes directly to leukemogenesis...

..Blood. 2001;97:3589-3595)..

..Two of 4 studies included in this analysis are registered at http://clinicaltrials.gov as NCT00002798 (CCG-2961) and NCT00070174 (COG AAML03P1)...

..However, five of six evaluable patients with colonies negative for monosomy 7 entered remission. These data support the hypothesis that leukaemic involvement of early progenitor cells affects the response to induction chemotherapy...

..24, P = .047). As CEBPA mutations are associated with lower relapse rate and improved survival, CEBPA mutation analysis needs to be incorporated into initial screening for risk identification and therapy allocation at diagnosis...

..The purpose of this chapter is to review the biology of receptor tyrosine kinases (RTKs) in AML, exploring how RTKs are being used as novel prognostic factors and potential therapeutic targets...

..Future studies will determine their potential role in leukemogenesis and their clinical significance...

..To evaluate the prognostic significance of the integrin cell adhesion molecule very late antigen-4 (VLA-4) in acute myeloid leukemia (AML)...

..002). This study suggests that FLT3/ITD involvement in CD34(+)/CD33(-) precursors is heterogeneous and that detection of the mutation in the less-mature progenitor population may be associated with disease resistance...

..Novel missense point mutations were found in exon 14, suggesting additional investigations should be performed in AML and other haematopoietic malignancies, using this sensitive technique...

..To analyze the prevalence and clinical implications of Wilms' tumor 1 (WT1) single nucleotide polymorphism (SNP) rs16754 in the context of other prognostic markers in pediatric acute myeloid leukemia (AML)...

..072) and RFS (estimated 5-year RFS: large = 13%, small = 27%, and no ITD = 34%, P = .017). These studies suggest that ITD size may have prognostic significance...

..After reviewing these two pathways, we explore some of the targeted therapies directed at these pathways that are under development for AML, many of which are already in clinical trials...

..Eleven patients (2.1%) harbored a novel V71I sequence alteration, which was found to be a germ-line polymorphism. IDH1 mutations were not detected in pediatric AML, and are uncommon in adult AML...

..This review evaluates prognostic factors in pediatric AML and discusses the feasibility of using these factors in risk-adapted therapy regimens...

..This review describes prognostic factors that play a major role in the outcome of children with AML and their potential use for treatment stratification in pediatric AML trials...

..The ability to achieve a durable second remission is complicated by toxicity and resistant disease. We report a novel combination of chemotherapy for relapsed pediatric ALL...

..However, poor outcomes in FLT3/ITD-positive patients could not be attributed to increased in vitro cellular drug resistance...

..We conclude that SHP-2 is an important cellular PTPase that is mutated in myeloid malignancies. Further investigation is required to clarify how these mutant proteins interact with Ras and other effectors to deregulate myeloid growth...

..Clinical testing of FLT3 inhibitors as molecularly targeted agents for the improvement of outcome of pediatric AML patients is warranted...

..0001). Thus, gene expression profiling identified AML patients with divergent prognoses within the FLT3-MU group, and the RUNX3 to ATRX expression ratio should be a useful prognostic indicator in these patients...

..NPMc(+) does not abrogate the negative prognostic influence of FLT3/ITD mutations, but may contribute to risk stratification in children who lack FLT3/ITD mutations by identifying a group with superior prognosis...

..Fewer black children than expected had an available family marrow donor...

..There was no significant outcome difference between DS-associated AML-M0 and non-M0 children. This study suggests that intensively treated non-DS-associated AML-M0 children have an inferior outcome compared with children with non-M0 AML...

..This grant project will undertake an extensive evaluation of Flt3 mutations in the largest patient population tested to date and will correlate the data with other biologic markers. ..

..With these enhancements and modifications, we believe we will be able to accurately predict relapse in more than 80% of children with AML who achieve remission. ..

..The data generated from this study will identify AML patients at high-risk of relapse early in the course of their disease, and will be used to guide therapy in risk-based approach in future trials. ..