|
|
Blood, 1 November 2004, Vol. 104, No. 9, pp. 2646-2654.
Prepublished online as a Blood First Edition Paper on July 13, 2004; DOI 10.1182/blood-2003-12-4449.
 Previous Article | Next Article 
Submitted January 6, 2004
Accepted March 30, 2004
Gene Expression Profiles at Diagnosis in de novo Childhood AML Patients Identify FLT3 Mutations with Good Clinical Outcomes
N J Lacayo, S Meshinchi, P Kinnunen, R Yu, Y Wang, C M Stuber, L Douglas, R Wahab, D L Becton, H Weinstein, M N Chang, C L Willman, J P Radich, R Tibshirani, Y Ravindranath, B Sikic, and G V Dahl*
Divisions of Pediatric Hematology/Oncology, Stanford University School of Medicine, Palo Alto, CA, USA; Children's Oncology Group, Arcadia, CA, USA
Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, USA; Children's Oncology Group, Arcadia, CA, USA
Divisions of Pediatric Hematology/Oncology, Stanford University School of Medicine, Palo Alto, CA, USA
Statistics, Stanford University School of Medicine, Palo Alto, CA, USA
Medical Oncology, Stanford University School of Medicine, Palo Alto, CA, USA
Arkansas Children's Hospital, Little Rock, AR, USA; Children's Oncology Group, Arcadia, CA, USA
Massachusetts General Hospital, Boston, MA, USA; Children's Oncology Group, Arcadia, CA, USA
Children's Oncology Group, Arcadia, CA, USA
Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, USA
Children's Hospital of Michigan, Detroit, MI, USA; Children's Oncology Group, Arcadia, CA, USA
* Corresponding author; email: gary.dahl{at}stanford.edu.
FLT3 mutations are associated with unfavorable outcomes in children with acute myeloid leukemia (AML). We used DNA microarrays to identify gene expression profiles related to FLT3 status and outcome in childhood AML. Among 81 diagnostic specimens, 36 had FLT3 mutations (FLT3-MU), 24 with internal tandem duplications (ITD) and 12 with activating loop mutations (ALM). In addition, eight of 19 specimens from patients with relapses had FLT3-MU. Predictive analysis of microarrays (PAM) identified genes that differentiated FLT3-ITD from FLT3-ALM and FLT3-WT cases. Among the 42 specimens with FLT3-MU, PAM identified 128 genes that correlated with clinical outcome. Event-free survival (EFS) in FLT3-MU patients with a favorable signature was 45% vs. 5% for those with an unfavorable signature (P = 0.018). Among FLT3-MU specimens, high expression of the RUNX3 gene and low expression of the ATRX gene were associated with inferior outcome. The ratio of RUNX3 to ATRX expression was used to classify FLT3-MU cases into three EFS groups: 70%, 37%, and 0% for low, intermediate, and high ratios (P < 0.0001). 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.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
Related Article in Blood Online:
-
Gene expression arrays and the therapist's dilemma
- A. Thomas Look
Blood 2004 104: 2611-2612.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
L. Bullinger, K. Dohner, R. Kranz, C. Stirner, S. Frohling, C. Scholl, Y. H. Kim, R. F. Schlenk, R. Tibshirani, H. Dohner, et al.
An FLT3 gene-expression signature predicts clinical outcome in normal karyotype AML
Blood,
May 1, 2008;
111(9):
4490 - 4495.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Brown, E. McIntyre, R. Rau, S. Meshinchi, N. Lacayo, G. Dahl, T. A. Alonzo, M. Chang, R. J. Arceci, and D. Small
The incidence and clinical significance of nucleophosmin mutations in childhood AML
Blood,
August 1, 2007;
110(3):
979 - 985.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. P. Steensma
The spectrum of molecular aberrations in myelodysplastic syndromes: in the shadow of acute myeloid leukemia
Haematologica,
June 1, 2007;
92(6):
723 - 727.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Meshinchi and R. J. Arceci
Prognostic Factors and Risk-Based Therapy in Pediatric Acute Myeloid Leukemia
Oncologist,
March 1, 2007;
12(3):
341 - 355.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. M. Bull, C. D. Coldren, M. W. Geraci, and N. F. Voelkel
Gene Expression Profiling in Pulmonary Hypertension
Proceedings of the ATS,
January 1, 2007;
4(1):
117 - 120.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Meshinchi, T. A. Alonzo, D. L. Stirewalt, M. Zwaan, M. Zimmerman, D. Reinhardt, G. J. L. Kaspers, N. A. Heerema, R. Gerbing, B. J. Lange, et al.
Clinical implications of FLT3 mutations in pediatric AML
Blood,
December 1, 2006;
108(12):
3654 - 3661.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. L. Brown, C. R. Wilkinson, S. R. Waterman, C. H. Kok, D. G. Salerno, S. M. Diakiw, B. Reynolds, H. S. Scott, A. Tsykin, G. F. Glonek, et al.
Genetic regulators of myelopoiesis and leukemic signaling identified by gene profiling and linear modeling
J. Leukoc. Biol.,
August 1, 2006;
80(2):
433 - 447.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. L. Stirewalt, K. J. Kopecky, S. Meshinchi, J. H. Engel, E. L. Pogosova-Agadjanyan, J. Linsley, M. L. Slovak, C. L. Willman, and J. P. Radich
Size of FLT3 internal tandem duplication has prognostic significance in patients with acute myeloid leukemia
Blood,
May 1, 2006;
107(9):
3724 - 3726.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Bullinger and P. J.M. Valk
Gene Expression Profiling in Acute Myeloid Leukemia
J. Clin. Oncol.,
September 10, 2005;
23(26):
6296 - 6305.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Sanoudou, E. Vafiadaki, D. A. Arvanitis, E. Kranias, and A. Kontrogianni-Konstantopoulos
Array lessons from the heart: focus on the genome and transcriptome of cardiomyopathies
Physiol Genomics,
April 14, 2005;
21(2):
131 - 143.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
