Size of FLT3 internal tandem duplication has prognostic significance in patients with acute myeloid leukemia

被引：178

作者：

Stirewalt, DL

Kopecky, KJ

Meshinchi, S

Engel, JH

Pogosova-Agadjanyan, EL

Linsley, J

Slovak, ML

Willman, CL

Radich, JP

机构：

[1] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA

[2] Fred Hutchinson Canc Res Ctr, SW Oncol Grp, Ctr Stat, Seattle, WA 98109 USA

[3] Univ Washington, Div Oncol, Seattle, WA 98195 USA

[4] Myeloid Dis Comm, Childrens Oncol Grp, Arcadia, CA USA

[5] Natl Med Ctr, Dept Cytogenet, Duarte, CA USA

[6] Univ New Mexico, Sch Med, Dept Pathol & Cell Biol, Albuquerque, NM 87131 USA

来源：

BLOOD | 2006年 / 107卷 / 09期

关键词：

D O I：

10.1182/blood-2005-08-3453

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

FLT3 internal tandem duplications (FLT3/ITDs) in the juxtamembrane domain are found in approximately 25% of acute myeloid leukemia (AML) patients, ranging in size from 3 to hundreds of nucleotides. We examined whether the sizes of FLT3/ITDs were associated with clinical outcomes in 151 AML patients enrolled in Southwest Oncology Group studies: S9333 and S9500. FLT3/ITDs were identified in 32% of patients (median ITD size = 39 nucleoticles; range, 15-153 nucleoticles). The CR rates were 35%, 67%, and 52% for patients with large (< 40), small (< 40), and no ITDs, respectively (P = .19). Increasing ITD size was associated with decreasing OS (estimated 5-year OS: large = 13%, small = 26%, and no ITD = 21%, P = .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.

引用

收藏

页码：3724 / 3726

页数：3

相关论文

共 24 条

[11] CORRELATION OF MULTIDRUG-RESISTANCE (MDR1) PROTEIN EXPRESSION WITH FUNCTIONAL DYE/DRUG EFFLUX IN ACUTE MYELOID-LEUKEMIA BY MULTIPARAMETER FLOW-CYTOMETRY - IDENTIFICATION OF DISCORDANT MDR(-)/EFFLUX(+) AND MDR1(+)/EFFLUX(-) CASES [J].

LEITH, CP ;

CHEN, IM ;

KOPECKY, KJ ;

APPELBAUM, FR ;

HEAD, DR ;

GODWIN, JE ;

WEICK, JK ;

WILLMAN, CL .

BLOOD, 1995, 86 (06) :2329-2342

[12] Activating mutations of RTK/ras signal transduction pathway in pediatric acute myeloid leukemia [J].

Meshinchi, S ;

Stirewalt, DL ;

Alonzo, TA ;

Zhang, QG ;

Sweetser, DA ;

Woods, WG ;

Bernstein, ID ;

Arceci, RJ ;

Radich, JP .

BLOOD, 2003, 102 (04) :1474-1479

[13] Prevalence and prognostic significance of Flt3 internal tandem duplication in pediatric acute myeloid leukemia [J].

Meshinchi, S ;

Woods, WG ;

Stirewalt, DL ;

Sweetser, DA ;

Buckley, JD ;

Tjoa, TK ;

Bernstein, ID ;

Radich, JP .

BLOOD, 2001, 97 (01) :89-94

[14] Flt3 mutations from patients with acute myeloid leukemia induce transformation of 32D cells mediated by the Ras and STAT5 pathways [J].

Mizuki, M ;

Fenski, R ;

Halfter, H ;

Matsumura, I ;

Schmidt, R ;

Müller, C ;

Grüning, R ;

Kratz-Abers, K ;

Serve, S ;

Steur, C ;

Büchner, T ;

Kienast, J ;

Kanakura, Y ;

Berdel, WE ;

Serve, H .

BLOOD, 2000, 96 (12) :3907-3914

[15]

PETERSDORF S, 1998, P AM SOC CLIN ONC LO, pA15

[16] Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia:: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease [J].

Schnittger, S ;

Schoch, C ;

Dugas, M ;

Kern, W ;

Staib, P ;

Wuchter, C ;

Löffler, H ;

Sauerland, CM ;

Serve, H ;

Büchner, T ;

Haferlach, T ;

Hiddemann, W .

BLOOD, 2002, 100 (01) :59-66

[17] A new and recurrent activating length mutation in exon 20 of the FLT3 gene in acute myeloid leukemia [J].

Spiekermann, K ;

Bagrintseva, K ;

Schoch, C ;

Haferlach, T ;

Hiddemann, W ;

Schnittger, S .

BLOOD, 2002, 100 (09) :3423-3425

[18] Novel FLT3 point mutations within exon 14 found in patients with acute myeloid leukaemia [J].

Stirewalt, DL ;

Meshinchi, S ;

Kussick, SJ ;

Sheets, KM ;

Pogosova-Agadjanyan, E ;

Willman, CL ;

Radich, JP .

BRITISH JOURNAL OF HAEMATOLOGY, 2004, 124 (04) :481-484

[19] FLT3, RAS, and TP53 mutations in elderly patients with acute myeloid leukemia [J].

Stirewalt, DL ;

Kopecky, KJ ;

Meshinchi, S ;

Appelbaum, FR ;

Slovak, ML ;

Willman, CL ;

Radich, JP .

BLOOD, 2001, 97 (11) :3589-3595

[20] Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia:: association with FAB subtypes and identification of subgroups with poor prognosis [J].

Thiede, C ;

Steudel, C ;

Mohr, B ;

Schaich, M ;

Schäkel, U ;

Platzbecker, U ;

Wermke, M ;

Bornhäuser, M ;

Ritter, M ;

Neubauer, A ;

Ehninger, G ;

Illmer, T .

BLOOD, 2002, 99 (12) :4326-4335