AML1-ETO collaborates with further genetic abnormalities to induce acute myeloid leukaemia (AML). We analysed 99 patients with an AML1-ETO rearrangement for additional aberrations. Frequent genetic abnormalities were, loss of a sex chromosome (56/99, 56·5%) and del(9)(q22) (24/99, 24·2%). The most frequent molecular aberrations were mutations of KITD816 (3/23, 13%) and NRAS (8/89, 8·9%). Further molecular abnormalities were FLT3 mutations (3/87, 3·4%), AML1 (1/26, 3·8%) and PU1 (1/14, 7·1%). MLL-PTD, KRAS and CEBPA mutations were not found. These clinical findings support the model that AML1-ETO collaborates with other genetic alterations, such as mutations of receptor tyrosine kinases, to induce AML.

References

Cairoli, R., Beghini, A., Grillo, G., Nadali, G., Elice, F., Ripamonti, C.B., Colapietro, P., Nichelatti, M., Pezzetti, L., Lunghi, M., Cuneo, A., Viola, A., Ferrara, F., Lazzarino, M., Rodeghiero, F., Pizzolo, G., Larizza, L. & Morra, E. (2005) Prognostic impact of c-KIT mutations in core binding factor leukemias. an Italian retrospective study. Blood, 107, 3463–3468.
10.1182/blood-2005-09-3640
PubMed Web of Science® Google Scholar
Gilliland, D.G. & Tallman, M.S. (2002) Focus on acute leukemias. Cancer Cell, 1, 417–420.
10.1016/S1535-6108(02)00081-8
CAS PubMed Web of Science® Google Scholar
ISCN (1995) Guidelines for Cancer Cytogenetics, Supplement to An International System for Human Cytogenetic Nomenclature. (ed. by F. Mitelman). S. Karger, Basel.
Google Scholar
Kuchenbauer, F., Feuring-Buske, M. & Buske, C. (2005) AML1-ETO needs a partner: new insights into the pathogenesis of t(8;21) leukemia. Cell Cycle, 4, 1716–1718.
10.4161/cc.4.12.2256
CAS PubMed Web of Science® Google Scholar
Mueller, B.U., Pabst, T., Osato, M., Asou, N., Johansen, L.M., Minden, M.D., Behre, G., Hiddemann, W., Ito, Y. & Tenen, D.G. (2002) Heterozygous PU.1 mutations are associated with acute myeloid leukemia. Blood, 100, 998–1007.
10.1182/blood.V100.3.998
CAS PubMed Web of Science® Google Scholar
Nakao, M., Janssen, J.W., Seriu, T. & Bartram, C.R. (2000) Rapid and reliable detection of N-ras mutations in acute lymphoblastic leukemia by melting curve analysis using LightCycler technology. Leukemia, 14, 312–315.
10.1038/sj.leu.2401645
CAS PubMed Web of Science® Google Scholar
Ono, R., Nakajima, H., Ozaki, K., Kumagai, H., Kawashima, T., Taki, T., Kitamura, T., Hayashi, Y. & Nosaka, T. (2005) Dimerization of MLL fusion proteins and FLT3 activation synergize to induce multiple-lineage leukemogenesis. Journal of Clinical Investigation, 115, 919–929.
10.1172/JCI200522725
CAS PubMed Web of Science® Google Scholar
Pabst, T., Mueller, B.U., Harakawa, N., Schoch, C., Haferlach, T., Behre, G., Hiddemann, W., Zhang, D.E. & Tenen, D.G. (2001) AML1-ETO downregulates the granulocytic differentiation factor C/EBPalpha in t(8;21) myeloid leukemia. Nature Medicine, 7, 444–451.
10.1038/86515
CAS PubMed Web of Science® Google Scholar
Schessl, C., Rawat, V.P., Cusan, M., Deshpande, A., Kohl, T.M., Rosten, P.M., Spiekermann, K., Humphries, R.K., Schnittger, S., Kern, W., Hiddemann, W., Quintanilla-Martinez, L., Bohlander, S.K., Feuring-Buske, M. & Buske, C. (2005) The AML1-ETO fusion gene and the FLT3 length mutation collaborate in inducing acute leukemia in mice. Journal of Clinical Investigation, 115, 2159–2168.
10.1172/JCI24225
CAS PubMed Web of Science® Google Scholar
Schlenk, R.F., Benner, A., Hartmann, F., Del Valle, F., Weber, C., Pralle, H., Fischer, J.T., Gunzer, U., Pezzutto, A., Weber, W., Grimminger, W., Preiss, J., Hensel, M., Frohling, S., Dohner, K., Haas, R., Dohner, H., & AML Study Group Ulm (AMLSG ULM) (2003) Risk-adapted postremission therapy in acute myeloid leukemia: results of the German multicenter AML HD93 treatment trial. Leukemia, 17, 1521–1528.
10.1038/sj.leu.2403009
CAS PubMed Web of Science® Google Scholar
Schnittger, S., Kohl, T.M., Haferlach, T., Kern, W., Hiddemann, W., Spiekermann, K. & Schoch, C. (2005) KIT-D816 mutations in AML1-ETO positive AML are associated with impaired event-free and overall survival. Blood, 107, 1791–1799.
10.1182/blood-2005-04-1466
PubMed Web of Science® Google Scholar
Yuan, Y., Zhou, L., Miyamoto, T., Iwasaki, H., Harakawa, N., Hetherington, C.J., Burel, S.A., Lagasse, E., Weissman, I.L., Akashi, K. & Zhang, D.E. (2001) AML1-ETO expression is directly involved in the development of acute myeloid leukemia in the presence of additional mutations. Proceedings of the National Academy of Science of the United States of America, 98, 10398–10403.
10.1073/pnas.171321298
CAS PubMed Web of Science® Google Scholar

Citing Literature

Volume134, Issue6

September 2006

Pages 616-619

Identification of additional cytogenetic and molecular genetic abnormalities in acute myeloid leukaemia with t(8;21)/AML1-ETO

Abstract

References

Citing Literature

References

Information

About Wiley Online Library

Help & Support

Opportunities

Connect with Wiley

Identification of additional cytogenetic and molecular genetic abnormalities in acute myeloid leukaemia with t(8;21)/AML1-ETO

Abstract

References

Citing Literature

References

Related

Information