|
|
Blood, 15 August 2007, Vol. 110, No. 4, pp. 1291-1300.
Prepublished online as a Blood First Edition Paper on May 7, 2007; DOI 10.1182/blood-2006-10-049783.
 Previous Article | Table of Contents | Next Article 
NEOPLASIA
Gene-expression profiling identifies distinct subclasses of core binding factor acute myeloid leukemia
Lars Bullinger1,
Frank G. Rücker1,
Stephan Kurz1,
Juan Du1,
Claudia Scholl1,
Sandrine Sander2,
Andrea Corbacioglu1,
Claudio Lottaz3,
Jürgen Krauter4,
Stefan Fröhling1,
Arnold Ganser4,
Richard F. Schlenk1,
Konstanze Döhner1,
Jonathan R. Pollack5, and
Hartmut Döhner1
1 Department of Internal Medicine III, University of Ulm, Ulm, Germany;
2 Department of Physiological Chemistry, University of Ulm, Ulm, Germany;
3 Department for Computational Molecular Biology, Max-Planck-Institute for Molecular Genetics, Berlin, Germany;
4 Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany; and
5 Department of Pathology, Stanford University, Palo Alto, CA
Core binding factor (CBF) leukemias, characterized by either inv(16)/t(16;16) or t(8;21), constitute acute myeloid leukemia (AML) subgroups with favorable prognosis. However, there exists substantial biologic and clinical heterogeneity within these cytogenetic groups that is not fully reflected by the current classification system. To improve the molecular characterization we profiled gene expression in a large series (n = 93) of AML patients with CBF leukemia [(inv (16), n = 55; t(8;21), n = 38)]. By unsupervised hierarchical clustering we were able to define a subgroup of CBF cases (n = 35) characterized by shorter overall survival times (P = .03). While there was no obvious correlation with fusion gene transcript levels, FLT3 tyrosine kinase domain, KIT, and NRAS mutations, the newly defined inv(16)/t(8;21) subgroup was associated with elevated white blood cell counts and FLT3 internal tandem duplications (P = .011 and P = .026, respectively). Supervised analyses of gene expression suggested alternative cooperating pathways leading to transformation. In the "favorable" CBF leukemias, antiapoptotic mechanisms and deregulated mTOR signaling and, in the newly defined "unfavorable" subgroup, aberrant MAPK signaling and chemotherapy-resistance mechanisms might play a role. While the leukemogenic relevance of these signatures remains to be validated, their existence nevertheless supports a prognostically relevant biologic basis for the heterogeneity observed in CBF leukemia.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
Y. Kuwatsuka, K. Miyamura, R. Suzuki, M. Kasai, A. Maruta, H. Ogawa, R. Tanosaki, S. Takahashi, K. Koda, K. Yago, et al.
Hematopoietic stem cell transplantation for core binding factor acute myeloid leukemia: t(8;21) and inv(16) represent different clinical outcomes
Blood,
February 26, 2009;
113(9):
2096 - 2103.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Heuser, D. B. Yap, M. Leung, T. R. de Algara, A. Tafech, S. McKinney, J. Dixon, R. Thresher, B. Colledge, M. Carlton, et al.
Loss of Mll5 results in pleiotropic hematopoietic defects, reduced neutrophil immune function, and extreme sensitivity to DNA demethylation
Blood,
February 12, 2009;
113(7):
1432 - 1443.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. J. Wouters, B. Lowenberg, and R. Delwel
A decade of genome-wide gene expression profiling in acute myeloid leukemia: flashback and prospects
Blood,
January 8, 2009;
113(2):
291 - 298.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Dimopoulos, M. A. Gertz, E. Kastritis, R. Garcia-Sanz, E. K. Kimby, V. LeBlond, J.-P. Fermand, G. Merlini, P. Morel, E. Morra, et al.
Update on Treatment Recommendations From the Fourth International Workshop on Waldenstrom's Macroglobulinemia
J. Clin. Oncol.,
January 1, 2009;
27(1):
120 - 126.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. G.W. Verhaak, B. J. Wouters, C. A.J. Erpelinck, S. Abbas, H. B. Beverloo, S. Lugthart, B. Lowenberg, R. Delwel, and P. J.M. Valk
Prediction of molecular subtypes in acute myeloid leukemia based on gene expression profiling
Haematologica,
January 1, 2009;
94(1):
131 - 134.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Sander, L. Bullinger, K. Klapproth, K. Fiedler, H. A. Kestler, T. F. E. Barth, P. Moller, S. Stilgenbauer, J. R. Pollack, and T. Wirth
MYC stimulates EZH2 expression by repression of its negative regulator miR-26a
Blood,
November 15, 2008;
112(10):
4202 - 4212.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. K. Cheng, L. Li, S. H. Cheng, K. M. Lau, N. P. H. Chan, R. S. M. Wong, M. M. K. Shing, C. K. Li, and M. H. L. Ng
Transcriptional repression of the RUNX3/AML2 gene by the t(8;21) and inv(16) fusion proteins in acute myeloid leukemia
Blood,
October 15, 2008;
112(8):
3391 - 3402.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Jongen-Lavrencic, S. M. Sun, M. K. Dijkstra, P. J. M. Valk, and B. Lowenberg
MicroRNA expression profiling in relation to the genetic heterogeneity of acute myeloid leukemia
Blood,
May 15, 2008;
111(10):
5078 - 5085.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Krejci, M. Wunderlich, H. Geiger, F.-S. Chou, D. Schleimer, M. Jansen, P. R. Andreassen, and J. C. Mulloy
p53 signaling in response to increased DNA damage sensitizes AML1-ETO cells to stress-induced death
Blood,
February 15, 2008;
111(4):
2190 - 2199.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
