Secondary genetic lesions in acute myeloid leukemia with inv(16) or t(16;16): a study of the German-Austrian AML Study Group (AMLSG)

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Item Type:	Article
Title:	Secondary genetic lesions in acute myeloid leukemia with inv(16) or t(16;16): a study of the German-Austrian AML Study Group (AMLSG)
Creators Name:	Paschka, P., Du, J., Schlenk, R.F., Gaidzik, V.I., Bullinger, L., Corbacioglu, A., Späth, D., Kayser, S., Schlegelberger, B., Krauter, J., Ganser, A., Köhne, C.H., Held, G., von Lilienfeld-Toal, M., Kirchen, H., Rummel, M., Götze, K., Horst, H.A., Ringhoffer, M., Lübbert, M., Wattad, M., Salih, H.R., Kündgen, A., Döhner, H. and Döhner, K.
Abstract:	In this study, we evaluated the impact of secondary genetic lesions in acute myeloid leukemia (AML) with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11. We studied 176 patients, all enrolled on prospective treatment trials, for secondary chromosomal aberrations and mutations in N-/KRAS, KIT, FLT3, and JAK2 (V617F) genes. Most frequent chromosomal aberrations were trisomy 22 (18%) and trisomy 8 (16%). Overall, 84% of patients harbored at least 1 gene mutation, with RAS being affected in 53% (45% NRAS; 13% KRAS) of the cases, followed by KIT (37%) and FLT3 (17%; FLT3-TKD [14%], FLT3-ITD [5%]). None of the secondary genetic lesions influenced achievement of complete remission. In multivariable analyses, KIT mutation (hazard ratio [HR] = 1.67; P = .04], log(10)(WBC) (HR = 1.33; P = .02), and trisomy 22 (HR = 0.54; P = .08) were relevant factors for relapse-free survival; for overall survival, FLT3 mutation (HR = 2.56; P = .006), trisomy 22 (HR = 0.45; P = .07), trisomy 8 (HR = 2.26; P = .02), age (difference of 10 years, HR = 1.46; P = .01), and therapy-related AML (HR = 2.13; P = .14) revealed as prognostic factors. The adverse effects of KIT and FLT3 mutations were mainly attributed to exon 8 and tyrosine kinase domain mutations, respectively. Our large study emphasizes the impact of both secondary chromosomal aberrations as well as gene mutations for outcome in AML with inv(16)/t (16;16).
Keywords:	Antineoplastic Combined Chemotherapy Protocols, Chromosome Aberrations, Chromosome Inversion, Pair 16 Human Chromosomes, Pair 22 Human Chromosomes, Pair 8 Human Chromosomes, Clinical Trials as Topic, Cohort Studies, ras Genes, Kaplan-Meier Estimate, Acute Myeloid Leukemia, Leukocyte Count, Multicenter Studies as Topic, Mutation, Second Primary Neoplasms, Fusion Oncogene Proteins, Prognosis, Proto-Oncogene Proteins c-kit, Trisomy, fms-Like Tyrosine Kinase 3
Source:	Blood
ISSN:	0006-4971
Publisher:	American Society of Hematology
Volume:	121
Number:	1
Page Range:	170-7
Date:	3 January 2013
Official Publication:	https://doi.org/10.1182/blood-2012-05-431486
PubMed:	View item in PubMed

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