The FLT3ITD mRNA level has a high prognostic impact in NPM1 mutated, but not in NPM1 unmutated, AML with a normal karyotype

被引:37
作者
Schneider, Friederike [1 ]
Hoster, Eva [1 ,2 ]
Unterhalt, Michael [1 ]
Schneider, Stephanie [1 ]
Dufour, Annika [1 ]
Benthaus, Tobias [1 ]
Mellert, Gudrun [1 ]
Zellmeier, Evelyn [1 ]
Kakadia, Purvi M. [1 ]
Bohlander, Stefan K. [1 ,3 ]
Feuring-Buske, Michaela [4 ]
Buske, Christian [5 ]
Braess, Jan [1 ]
Heinecke, Achim [6 ]
Sauerland, Maria C. [6 ]
Berdel, Wolfgang E. [7 ]
Buechner, Thomas [7 ]
Woermann, Bernhard J. [8 ]
Hiddemann, Wolfgang [1 ,3 ]
Spiekermann, Karsten [1 ,3 ]
机构
[1] Univ Hosp Munich, Dept Med 3, Lab Leukemia Diagnost, Munich, Germany
[2] Univ Munich, Inst Med Stat Biometry & Epidemiol, Munich, Germany
[3] Helmholtz Ctr Munich, Clin Cooperat Grp Acute Leukemias, Munich, Germany
[4] Univ Ulm, Dept Internal Med 3, D-7900 Ulm, Germany
[5] Inst Expt Tumor Res, Comprehens Canc Ctr Ulm, Ulm, Germany
[6] Univ Munster, Inst Biostat & Clin Res, Munster, Germany
[7] Univ Munster, Dept Med Hematol & Oncol, Munster, Germany
[8] German Soc Hematol & Oncol, Berlin, Germany
关键词
ACUTE MYELOID-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; GENE-MUTATIONS; NUCLEOPHOSMIN; CYTOGENETICS;
D O I
10.1182/blood-2010-12-327072
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The impact of a FLT3-internal tandem duplication (FLT3ITD) on prognosis of patients with acute myeloid leukemia (AML) is dependent on the ratio of mutated to wild-type allele. In 648 normal karyotype (NK) AML patients, we found a significant independent effect of the quantitative FLT3ITD mRNA level-measured as (FLT3ITD/wtFLT3)/(FLT3ITD/wtFLT3 + 1)-on outcome. Moreover, this effect was clearly seen in 329 patients with a mutated NPM1 gene (NPM1(+)), but not in 319 patients without a NPM1 mutation (wtNPM1). In a multivariate Cox regression model, the quantitative FLT3ITD mRNA level showed an independent prognostic impact on overall survival (OS) and relapse-free survival (RFS) only in the NPM1(+) subgroup (OS: hazard ratio, 5.9; [95% confidence interval [CI]: 3.1-11.2]; RFS: hazard ratio, 7.5 [95% CI: 3.4-16.5]). The FLT3ITD mRNA level contributes to relapse risk stratification and might help to guide postremission therapy in NPM1-mutated AML. (Blood. 2012;119(19):4383-4386)
引用
收藏
页码:4383 / 4386
页数:4
相关论文
共 14 条
[1]  
[Anonymous], 2008, WHO CLASSIFICATION T
[2]   Rapid and sensitive screening for CEBPA mutations in acute myeloid leukaemia [J].
Benthaus, Tobias ;
Schneider, Friederike ;
Mellert, Gudrun ;
Zellmeier, Evelyn ;
Schneider, Stephanie ;
Kakadia, Purvi M. ;
Hiddemann, Wolfgang ;
Bohlander, Stefan K. ;
Feuring-Buske, Michaela ;
Braess, Jan ;
Spiekermann, Karsten ;
Dufour, Annika .
BRITISH JOURNAL OF HAEMATOLOGY, 2008, 143 (02) :230-239
[3]   Double induction containing either two courses or one course of high-dose cytarabine plus mitoxantrone and postremission therapy by either autologous stem-cell transplantation or by prolonged maintenance for acute myeloid leukemia [J].
Büchner, T ;
Berdel, WE ;
Schoch, C ;
Haferlach, T ;
Serve, HL ;
Kienast, J ;
Schnittger, S ;
Kern, W ;
Tchinda, J ;
Reichle, A ;
Lengfelder, E ;
Staib, P ;
Ludwig, WD ;
Aul, C ;
Eimermacher, H ;
Balleisen, L ;
Sauerland, MC ;
Heinecke, A ;
Wöermann, B ;
Hiddemann, W .
JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (16) :2480-2489
[4]   Age-Related Risk Profile and Chemotherapy Dose Response in Acute Myeloid Leukemia: A Study by the German Acute Myeloid Leukemia Cooperative Group [J].
Buechner, Thomas ;
Berdel, Wolfgang E. ;
Haferlach, Claudia ;
Haferlach, Torsten ;
Schnittger, Susanne ;
Mueller-Tidow, Carsten ;
Braess, Jan ;
Spiekermann, Karsten ;
Kienast, Joachim ;
Staib, Peter ;
Grueneisen, Andreas ;
Kern, Wolfgang ;
Reichle, Albrecht ;
Maschmeyer, Georg ;
Aul, Carlo ;
Lengfelder, Eva ;
Sauerland, Maria-Cristina ;
Heinecke, Achim ;
Woermann, Bernhard ;
Hiddemann, Wolfgang .
JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (01) :61-69
[5]   Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet [J].
Doehner, Hartmut ;
Estey, Elihu H. ;
Amadori, Sergio ;
Appelbaum, Frederick R. ;
Buechner, Thomas ;
Burnett, Alan K. ;
Dombret, Herve ;
Fenaux, Pierre ;
Grimwade, David ;
Larson, Richard A. ;
Lo-Coco, Francesco ;
Naoe, Tomoki ;
Niederwieser, Dietger ;
Ossenkoppele, Gert J. ;
Sanz, Miguel A. ;
Sierra, Jorge ;
Tallman, Martin S. ;
Loewenberg, Bob ;
Bloomfield, Clara D. .
BLOOD, 2010, 115 (03) :453-474
[6]   Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics:: interaction with other gene mutations [J].
Döhner, K ;
Schlenk, RF ;
Habdank, M ;
Scholl, C ;
Rücker, FG ;
Corbacioglu, A ;
Bullinger, L ;
Fröhling, S ;
Döhner, H .
BLOOD, 2005, 106 (12) :3740-3746
[7]   Acute Myeloid Leukemia With Biallelic CEBPA Gene Mutations and Normal Karyotype Represents a Distinct Genetic Entity Associated With a Favorable Clinical Outcome [J].
Dufour, Annika ;
Schneider, Friederike ;
Metzeler, Klaus H. ;
Hoster, Eva ;
Schneider, Stephanie ;
Zellmeier, Evelyn ;
Benthaus, Tobias ;
Sauerland, Maria-Cristina ;
Berdel, Wolfgang E. ;
Buechner, Thomas ;
Woermann, Bernhard ;
Braess, Jan ;
Hiddemann, Wolfgang ;
Bohlander, Stefan K. ;
Spiekermann, Karsten .
JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (04) :570-577
[8]   Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. [J].
Falini, B ;
Mecucci, C ;
Tiacci, E ;
Alcalay, M ;
Rosati, R ;
Pasqualucci, L ;
La Starza, R ;
Diverio, D ;
Colombo, E ;
Santucci, A ;
Bigerna, B ;
Pacini, R ;
Pucciarini, A ;
Liso, A ;
Vignetti, M ;
Fazi, P ;
Meani, N ;
Pettirossi, V ;
Saglio, G ;
Mandelli, F ;
Lo-Coco, F ;
Pelicci, P ;
Martelli, MF .
NEW ENGLAND JOURNAL OF MEDICINE, 2005, 352 (03) :254-266
[9]   Clinical implications of FLT3 mutations in pediatric AML [J].
Meshinchi, Soheil ;
Alonzo, Todd A. ;
Stirewalt, Derek L. ;
Zwaan, Michel ;
Zimmerman, Martin ;
Reinhardt, Dirk ;
Kaspers, Gertjan J. L. ;
Heerema, Nyla A. ;
Gerbing, Robert ;
Lange, Beverly J. ;
Radich, Jerald P. .
BLOOD, 2006, 108 (12) :3654-3661
[10]   Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia [J].
Schlenk, Richard F. ;
Doehner, Konstanze ;
Krauter, Juergen ;
Froehling, Stefan ;
Corbacioglu, Andrea ;
Bullinger, Lars ;
Habdank, Marianne ;
Spaeth, Daniela ;
Morgan, Michael ;
Benner, Axel ;
Schlegelberger, Brigitte ;
Heil, Gerhard ;
Ganser, Arnold ;
Doehner, Hartmut .
NEW ENGLAND JOURNAL OF MEDICINE, 2008, 358 (18) :1909-1918