Independent confirmation of a prognostic gene-expression signature in adult acute myeloid leukemia with a normal karyotype: a Cancer and Leukemia Group B study - PubMed (original) (raw)
Multicenter Study
. 2006 Sep 1;108(5):1677-83.
doi: 10.1182/blood-2006-02-005538. Epub 2006 May 2.
Guido Marcucci, Amy S Ruppert, Krzysztof Mrózek, Susan P Whitman, James W Vardiman, Peter Paschka, Tamara Vukosavljevic, Claudia D Baldus, Jonathan E Kolitz, Michael A Caligiuri, Richard A Larson, Clara D Bloomfield; Cancer and Leukemia Group B
Affiliations
- PMID: 16670265
- PMCID: PMC1895508
- DOI: 10.1182/blood-2006-02-005538
Multicenter Study
Independent confirmation of a prognostic gene-expression signature in adult acute myeloid leukemia with a normal karyotype: a Cancer and Leukemia Group B study
Michael D Radmacher et al. Blood. 2006.
Abstract
Patients with acute myeloid leukemia (AML) and normal karyotype are classified in an intermediate-risk group, albeit this subset is heterogeneous for clinical outcome. A recent complementary DNA microarray study identified a gene-expression signature that--when used to cluster normal karyotype patients--separated them into 2 prognostically relevant subgroups. We sought the first independent validation of the prognostic value of this signature. Using oligonucleotide microarrays to measure gene expression in samples from uniformly treated adults with karyotypically normal AML, we performed cluster analysis based on the previously identified signature. We also developed a well-defined classification rule using the signature to predict outcome for individual patients. Cluster analysis confirmed the prognostic utility of the signature: patient clusters differed in overall (P = .001) and disease-free (P = .001) survival. The signature-based classifier identified groups with differences in overall (P = .02) and disease-free (P = .05) survival. A strong association of the outcome classifier with the prognostically adverse FLT3 internal tandem duplication (FLT3 ITD) potentially explained the prognostic significance of the signature. However, in the subgroup of patients without FLT3 ITD there was a moderate difference in survival for the classifier-derived groups. Our analysis confirms the applicability of the gene-expression profiling strategy for outcome prediction in cytogenetically normal AML.
Figures
Figure 1.
Prognostic significance of signature-based clusters in cytogenetically normal AML. (A) The Bullinger validation signature dichotomized uniformly treated CALGB patients with cytogenetically normal AML into 2 distinct clusters. Patients included in cluster I had a worse overall (B) and disease-free (C) survival compared with those in cluster II.
Figure 2.
Compound covariate prediction (CCP) algorithm predicts outcome for individual patients. Overall (A) and disease-free (B) survival according to CCP class membership. Accuracy rates of the signature-based CCP classifier for overall (C) and disease-free (D) survival.
Figure 3.
Interaction between FLT3 ITD status and CCP class membership. (A) Overall (i) and disease-free (ii) survival for patients with FLT3 ITD according to poor and good CCP class membership. (B) Overall (i) and disease-free (ii) survival for patients with wild-type FLT3 according to poor and good CCP class membership.
Similar articles
- Risk assessment in patients with acute myeloid leukemia and a normal karyotype.
Bienz M, Ludwig M, Leibundgut EO, Mueller BU, Ratschiller D, Solenthaler M, Fey MF, Pabst T. Bienz M, et al. Clin Cancer Res. 2005 Feb 15;11(4):1416-24. doi: 10.1158/1078-0432.CCR-04-1552. Clin Cancer Res. 2005. PMID: 15746041 - Use of gene-expression profiling to identify prognostic subclasses in adult acute myeloid leukemia.
Bullinger L, Döhner K, Bair E, Fröhling S, Schlenk RF, Tibshirani R, Döhner H, Pollack JR. Bullinger L, et al. N Engl J Med. 2004 Apr 15;350(16):1605-16. doi: 10.1056/NEJMoa031046. N Engl J Med. 2004. PMID: 15084693 - Overexpression of the ETS-related gene, ERG, predicts a worse outcome in acute myeloid leukemia with normal karyotype: a Cancer and Leukemia Group B study.
Marcucci G, Baldus CD, Ruppert AS, Radmacher MD, Mrózek K, Whitman SP, Kolitz JE, Edwards CG, Vardiman JW, Powell BL, Baer MR, Moore JO, Perrotti D, Caligiuri MA, Carroll AJ, Larson RA, de la Chapelle A, Bloomfield CD. Marcucci G, et al. J Clin Oncol. 2005 Dec 20;23(36):9234-42. doi: 10.1200/JCO.2005.03.6137. Epub 2005 Nov 7. J Clin Oncol. 2005. PMID: 16275934 - Influence of new molecular prognostic markers in patients with karyotypically normal acute myeloid leukemia: recent advances.
Mrózek K, Döhner H, Bloomfield CD. Mrózek K, et al. Curr Opin Hematol. 2007 Mar;14(2):106-14. doi: 10.1097/MOH.0b013e32801684c7. Curr Opin Hematol. 2007. PMID: 17255787 Review. - Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: are we ready for a prognostically prioritized molecular classification?
Mrózek K, Marcucci G, Paschka P, Whitman SP, Bloomfield CD. Mrózek K, et al. Blood. 2007 Jan 15;109(2):431-48. doi: 10.1182/blood-2006-06-001149. Epub 2006 Sep 7. Blood. 2007. PMID: 16960150 Free PMC article. Review.
Cited by
- Favorable prognostic impact of NPM1 mutations in older patients with cytogenetically normal de novo acute myeloid leukemia and associated gene- and microRNA-expression signatures: a Cancer and Leukemia Group B study.
Becker H, Marcucci G, Maharry K, Radmacher MD, Mrózek K, Margeson D, Whitman SP, Wu YZ, Schwind S, Paschka P, Powell BL, Carter TH, Kolitz JE, Wetzler M, Carroll AJ, Baer MR, Caligiuri MA, Larson RA, Bloomfield CD. Becker H, et al. J Clin Oncol. 2010 Feb 1;28(4):596-604. doi: 10.1200/JCO.2009.25.1496. Epub 2009 Dec 21. J Clin Oncol. 2010. PMID: 20026798 Free PMC article. - Tipifarnib in the treatment of newly diagnosed acute myelogenous leukemia.
Karp JE, Lancet JE. Karp JE, et al. Biologics. 2008 Sep;2(3):491-500. doi: 10.2147/btt.s3485. Biologics. 2008. PMID: 19707379 Free PMC article. - An 86-probe-set gene-expression signature predicts survival in cytogenetically normal acute myeloid leukemia.
Metzeler KH, Hummel M, Bloomfield CD, Spiekermann K, Braess J, Sauerland MC, Heinecke A, Radmacher M, Marcucci G, Whitman SP, Maharry K, Paschka P, Larson RA, Berdel WE, Büchner T, Wörmann B, Mansmann U, Hiddemann W, Bohlander SK, Buske C; Cancer and Leukemia Group B; German AML Cooperative Group. Metzeler KH, et al. Blood. 2008 Nov 15;112(10):4193-201. doi: 10.1182/blood-2008-02-134411. Epub 2008 Aug 20. Blood. 2008. PMID: 18716133 Free PMC article. Clinical Trial. - Micro-RNAs and copy number changes: new levels of gene regulation in acute myeloid leukemia.
Larson RA. Larson RA. Chem Biol Interact. 2010 Mar 19;184(1-2):21-5. doi: 10.1016/j.cbi.2009.10.002. Epub 2009 Oct 12. Chem Biol Interact. 2010. PMID: 19822134 Free PMC article. - Sp1/NFkappaB/HDAC/miR-29b regulatory network in KIT-driven myeloid leukemia.
Liu S, Wu LC, Pang J, Santhanam R, Schwind S, Wu YZ, Hickey CJ, Yu J, Becker H, Maharry K, Radmacher MD, Li C, Whitman SP, Mishra A, Stauffer N, Eiring AM, Briesewitz R, Baiocchi RA, Chan KK, Paschka P, Caligiuri MA, Byrd JC, Croce CM, Bloomfield CD, Perrotti D, Garzon R, Marcucci G. Liu S, et al. Cancer Cell. 2010 Apr 13;17(4):333-47. doi: 10.1016/j.ccr.2010.03.008. Cancer Cell. 2010. PMID: 20385359 Free PMC article.
References
- Mrózek K, Heerema NA, Bloomfield CD. Cytogenetics in acute leukemia. Blood Rev. 2004;18: 115-136. - PubMed
- Byrd JC, Mrózek K, Dodge RK, et al. Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood. 2002;100: 4325-4336. - PubMed
- Grimwade D, Walker H, Harrison G, et al. The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial. Blood. 2001;98: 1312-1320. - PubMed
- Slovak ML, Kopecky KJ, Cassileth PA, et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group study. Blood. 2000;96: 4075-4083. - PubMed
- Marcucci G, Mrózek K, Bloomfield CD. Molecular heterogeneity and prognostic biomarkers in adults with acute myeloid leukemia and normal cytogenetics. Curr Opin Hematol. 2005;12: 68-75. - PubMed
Publication types
MeSH terms
Grants and funding
- CA 09512/CA/NCI NIH HHS/United States
- CA 77658/CA/NCI NIH HHS/United States
- CA 31946/CA/NCI NIH HHS/United States
- CA 16058/CA/NCI NIH HHS/United States
- CA 102031/CA/NCI NIH HHS/United States
- CA 101140/CA/NCI NIH HHS/United States
- CA 90469/CA/NCI NIH HHS/United States
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous