NPM1 but not FLT3-ITD mutations predict early blast cell clearance and CR rate in patients with normal karyotype AML (NK-AML) or high-risk myelodysplastic syndrome (MDS)

Blood

Volumn 113, Issue 21, 2009, Pages 5250-5253

  Schneider, Friederike ^a   Hoster, Eva ^a   Unterhalt, Michael ^e   Schneider, Stephanie ^a   Dufour, Annika ^a   Benthaus, Tobias ^a   Mellert, Gudrun ^a   Zellmeier, Evelin ^a   Bohlander, Stefan K ^a,b   Feuring Buske, Michaela ^a,b   Buske, Christian ^a,b   Braess, Jan ^a   Fritsch, Susanne ^a   Heinecke, Achim ^c   Sauerland, Maria C ^c   Berdel, Wolfgang E ^c   Buechner, Thomas ^c   Woermann, Bernhard J ^d   Hiddemann, Wolfgang ^a,b   Spiekermann, Karsten ^a,b  

^a LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^b INSTITUTE OF EPIDEMIOLOGY   (Germany)

^c UNIVERSITY OF MÜNSTER   (Germany)

^d KLINIKUM BRAUNSCHWEIG   (Germany)

^e NONE

Author keywords

[No Author keywords available]

Indexed keywords

CD135 ANTIGEN; MUTANT PROTEIN; NUCLEOPHOSMIN; ANTINEOPLASTIC AGENT; FLT3 PROTEIN, HUMAN; NUCLEAR PROTEIN;

ACUTE GRANULOCYTIC LEUKEMIA; ARTICLE; BLAST CELL; CANCER REGRESSION; GENE MUTATION; HIGH RISK PATIENT; HUMAN; IN VIVO STUDY; KARYOTYPE; MAJOR CLINICAL STUDY; MYELODYSPLASTIC SYNDROME; OUTCOME ASSESSMENT; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROGNOSIS; BLAST CELL CRISIS; GENETICS; INVERTED REPEAT; KARYOTYPING; MUTATION; NATURAL KILLER CELL; PATHOLOGY; REMISSION;

ANTINEOPLASTIC AGENTS; BLAST CRISIS; FMS-LIKE TYROSINE KINASE 3; HUMANS; INVERTED REPEAT SEQUENCES; KARYOTYPING; KILLER CELLS, NATURAL; LEUKEMIA, MYELOID, ACUTE; MUTATION; MYELODYSPLASTIC SYNDROMES; NUCLEAR PROTEINS; PROGNOSIS; REMISSION INDUCTION;

EID: 67149084950     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2008-09-172668     Document Type: Article

References (18)

1. Schnittger S, Schoch C, Kern W, et al. Nucleophosmin gene mutations are predictors of favorable prognosis in acute myelogenous leukemia with a normal karyotype. Blood. 2005;106:3733-3739. (Pubitemid 41739006)
2. Falini B, Mecucci C, Tiacci E, et al. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med. 2005;352:254-266. (Pubitemid 40110814)
3. Döhner K, Schlenk RF, Habdank M, et al. Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics: interaction with other gene mutations. Blood. 2005;106:3740-3746. (Pubitemid 41739007)
4. Verhaak RG, Goudswaard CS, van Putten W, et al. Mutations in nucleophosmin (NPM1) in acute myeloid leukemia (AML): association with other gene abnormalities and previously established gene expression signatures and their favorable prognostic significance. Blood. 2005;106:3747-3754.
5. Pabst T, Mueller BU, Harakawa N, et al. AML1- ETO downregulates the granulocytic differentiation factor C/EBPalpha in t(8;21) myeloid leukemia. Nat Med. 2001;7:444-451. (Pubitemid 32298547)
6. Boissel N, Renneville A, Biggio V, et al. Prevalence, clinical profile, and prognosis of NPM mutations in AML with normal karyotype. Blood. 2005;106:3618-3620. (Pubitemid 41609201)
7. Fröhling S, Schlenk RF, Stolze I, et al. CEBPA mutations in younger adults with acute myeloid leukemia and normal cytogenetics: prognostic relevance and analysis of cooperating mutations. J Clin Oncol. 2004;22:624-633. (Pubitemid 41095065)
8. Whitman SP, Ruppert AS, Radmacher MD, et al. FLT3 D835/I836 mutations are associated with poor disease-free survival and a distinct gene-expression signature among younger adults with de novo cytogenetically normal acute myeloid leukemia lacking FLT3 internal tandem duplications. Blood. 2008;111:1552-1559.
9. Mrozek K, Marcucci G, Paschka P, Whitman SP, Bloomfield CD. 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? Blood. 2007;109:431-448.
10. Kern W, Haferlach T, Schoch C, et al. Early blast clearance by remission induction therapy is a major independent prognostic factor for both achievement of complete remission and long-term outcome in acute myeloid leukemia: data from the German AML Cooperative Group (AMLCG) 1992 Trial. Blood. 2003;101:64-70. (Pubitemid 36025888)
11. Büchner T, Berdel WE, Schoch C, et al. 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 Clin Oncol. 2006;24:2480-2489. (Pubitemid 46655599)
12. Haferlach T, Schoch C, Loffler H, et al. Morphologic dysplasia in de novo acute myeloid leukemia (AML) is related to unfavorable cytogenetics but has no independent prognostic relevance under the conditions of intensive induction therapy: results of a multiparameter analysis from the German AML Cooperative Group studies. J Clin Oncol. 2003;21:256-265. (Pubitemid 46606154)
13. Schnittger S, Schoch C, Dugas M, et al. 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. Blood. 2002;100:59-66.
14. Clayton D, Hills M. Choice and Interpretation of Models: Statistical models in Epidemiology. Vol 1. Oxford, United Kingdom: Oxford Science Publications; 1993.
15. Marubini E, Valsecchi MG. Analysing Survival Data from Clinical Trials and Observational Studies Statistics in Practice. New York, NY: John Wiley & Sons; 1995.
16. + AML): biologic and clinical features. Blood. 2007;109:874-885.
17. Cilloni D, Messa F, Rosso V, et al. Increase sensitivity to chemotherapeutical agents and cytoplasmatic interaction between NPM leukemic mutant and NF-kappaB in AML carrying NPM1 mutations. Leukemia. 2008;22:1234-1240. (Pubitemid 351833792)
18. Guzman ML, Neering SJ, Upchurch D, et al. Nuclear factor-kappaB is constitutively activated in primitive human acute myelogenous leukemia cells. Blood. 2001;98:2301-2307.