K. J. Ahn

Non-A type nucleophosmin 1 gene mutation predicts poor clinical outcome in de novo adult acute myeloid leukemia: differential clinical importance of NPM1 mutation according to subtype

Mutations of nucleophosmin gene (NPM1) are known to be related to good prognosis in AML patients lacking FLT3 internal tandem duplication (FLT3-ITD). Recently, NPM1 mutations other than type A were reported, but their clinical significance is not well known. Retrospective medical record review of 106 de novo AML patients lacking FLT3-ITD, who received induction chemotherapy from three centers in Korea between 1997 and 2007, was performed. Direct sequencing of NPM1 and RT-PCR for FLT3-ITD was performed on genomic DNA derived from blood samples of patients before induction chemotherapy for detection of mutations. NPM1 mutation was detected in 18 patients, where 13 were type A mutants and 5 were non-type A mutants. CR, CR1-D and OS was not different according to NPM1 mutational status overall. But, non-type A NPM1 mutation was related to shorter CR1-D when compared with NPM1 wild types and NPM1 type A mutation (p = 0.004). OS was shorter in non-type A mutants when compared with NPM1 wild-type patients and NPM1 type A mutants (p = 0.001). The type of mutation of NPM1 is important for prognosis in de novo AML lacking FLT3-ITD. Non-A type NPM1 mutation is a poor prognostic factor.

Different clinical importance of FLT3 internal tandem duplications in AML according to FAB classification: possible existence of distinct leukemogenesis involving monocyte differentiation pathway

Impact of FLT3 receptor tyrosine kinase activation via internal tandem duplication (ITD) of the juxtamembrane region on outcome of acute myeloid leukemia (AML) is still controversial. Recent researches reveal a role of FLT3 in monocyte differentiation in hematopoiesis. We analyzed the clinical impact of FLT3 alterations in adult AML patients excluding acute promyelocytic leukemia (APL) who received induction chemotherapy according to morphologic classification. Retrospective review of medical records from three centers in Korea between 1997 and 2007 was performed. Polymerase chain reaction was performed on genomic DNA derived from blood samples of patients before induction chemotherapy for FLT3-ITD detection. We assessed overall survival (OS), first disease-free survival (1-DFS), and response to induction chemotherapy. One hundred eighty-four patients (median age 49.1xa0years, range 16.0–76.5) with AML excluding APL received induction chemotherapy from three centers. FLT3-ITD was detected in 22 patients. One hundred forty-one patients were below age 60. One hundred seventy-nine patients received induction chemotherapy with cytarabine and idarubicin (AId) regimen. One hundred nineteen patients achieved complete remission (CR) after first induction chemotherapy. FLT3-ITD was not related to achievement of CR. 1-DFS was longer in patients without FLT3-ITD (median 1-DFS 16.5 vs. 8.5xa0months, pu2009=u20090.025). 1-DFS was not different according to FLT3-ITD status in nonmonocyte lineage leukemia (pu2009=u20090.355), while 1-DFS was shorter in monocyte lineage leukemia for FLT3-ITD positive patients (20.9 vs. 2.4xa0months, pu2009<u20090.001). FLT3-ITD had no impact on OS except for monocyte lineage, where OS was significantly shorter in FLT3-ITD positive group (39.4 vs. 6.0xa0months, pu2009=u20090.026). Moreover FLT3-ITD was stronger prognostic factors in monocyte lineage AML than risk stratification based on cytogenetics. Status of FLT3-ITD should be analyzed differently in AML patients according to morphologic profile. FLT3-ITD is a predictive and prognostic marker only in monocyte lineage patients. This result suggests an existence of distinct subset of monocyte lineage AML with leukemogenesis involving FLT3 activating pathway.

Abstract 1742: Suppression of Akt activity selectively induced apoptosis of Ara-C resistant AML cells

Treatment outcome of acute myeloid leukemia (AML), intensive Ara-C chemotherapy, remains unsatisfactory. It has been shown that the frequency of relapse is high and only 20 to 30% rate of the overall five year survival. Ara-C resistance could be one of major factors in decreasing the efficacy of intensive Ara-C chemotherapy. In this study, we established in vitro Ara-C resistant AML cell lines (KG1 and ML-1) and examined to ascertain the cause of Ara-C resistance. The expression levels of CDA in Ara-C resistant cell lines were higher than in parental cell line. However, the expression of other genes was not significantly different. Besides, PI3K/AKT was persistantly activated in Ara-C resistant cell lines. Also, mTOR, downstream of AKT, was highly expressed in AML resistant cell lines. MTT assay showed that PI3K specific inhbitor, LY29002, and mTOR inhibitor, rapamycin, inhibited the growth of AML cells and there was no different among AML cells. A synergic effect of Ara-C induced apoptosis was not detected in AML cells co-treated with rapamycin. Nevertheless, LY29002 and rapamycin was more effective to induce apoptosis in Ara-C resistant AML cell lines. Our data indicated that persistent activation of Akt in AML cells contributed to becoming resistant to Arc-C treatments. Inhibition of Akt activation would be a potential target to overcome Ara-C resistance in AML. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1742. doi:10.1158/1538-7445.AM2011-1742

Ultrabroadband metamaterial with full transmission control

We study log periodic nanoresonators on VO2 thin film, amplifying available dynamic range for extinction and transmission. Over 1,000:1 extinction ratio for the nano-pattern is achieved when the film undergoes insulator-to-metal phase transition, compared with 10:1 ratio for the unpatterned cases.

Tight-binding description of transmission through crowded terahertz nanoresonators

We present resonant transmission through rectangular hole array on a metallic film. Transmission spectra broaden with the resonance peaks shifting toward higher frequencies, as the period decreases. The broadening is caused by inter-resonator coupling effects similar to the tight binding model.

Resonance frequency shifts of rectangular holes on finite dielectric substrates

We observe that rectangular holes fabricated in a gold film with a sub-skindepth thickness show blue-shifted resonance frequencies as the width increases. For rectangular holes on a finite substrate its thickness and the hole width are crucial factors determining the resonance frequency.

Pinch harmonic analogue of terahertz nanoresonator control using metal nanorods

We demonstrate that platinum nanorods across the gap of a nanoresonator shift or overdamp the resonance depending on the rod-size. Moreover, what is striking is that the thinner nanorods almost completely turn off both the fundamental and higher mode resonances, analogous to the pinch harmonics.