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Identification of distinct molecular phenotypes in acute megakaryoblastic leukemia by gene expression profiling
被引:152
作者:
Bourquin, JP
Subramanian, A
Langebrake, C
Reinhardte, D
Bernard, O
Ballerini, P
Baruchel, A
Cavé, H
Dastugue, N
Hasle, H
Kaspers, GL
Lessard, M
Michaux, L
Vyas, P
van Wering, E
Zwaan, CM
Golub, TR
Orkin, SH
[1
]
机构:
[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA
[3] MIT, Broad Inst, Cambridge, MA 02141 USA
[4] Harvard Univ, Cambridge, MA 02141 USA
[5] Hannover Med Sch, D-30625 Hannover, Germany
[6] Hop Necker Enfants Malad, INSERM, F-75015 Paris, France
[7] Hop Trousseau, Serv Hematol Biol, F-75012 Paris, France
[8] Hop St Louis, Cent Hematol Lab, Serv Hematol Pediat & Adulte, F-75010 Paris, France
[9] Hop Robert Debre, Lab Biochim Genet, F-75019 Paris, France
[10] Hop Purpan, Hematol Lab, F-31059 Toulouse, France
[11] Aarhus Univ, Skejby Hosp, DK-8200 Aarhus N, Denmark
[12] Vrije Univ Amsterdam, Med Ctr, Dept Pediat Hematol Oncol, NL-1007 MB Amsterdam, Netherlands
[13] Hop Univ Strasbourg, Hop Hautepierre, Hematol Lab, F-67098 Strasbourg, France
[14] Clin Univ St Luc, B-1200 Brussels, Belgium
[15] Dutch Childhood Oncol Grp, The Hague, Netherlands
[16] Oxford Radcliffe Hosp, Dept Haematol, Oxford OX3 9DU, England
[17] Erasmus Med Ctr, Dept Pediat Oncol, NL-3000 CB Rotterdam, Netherlands
[18] Univ Zurich, Kinderklin, Dept Pediat Oncol, CH-8032 Zurich, Switzerland
来源:
关键词:
Down syndrome;
GATA1;
D O I:
10.1073/pnas.0511150103
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
Individuals with Down syndrome (DS) are predisposed to develop acute megakaryoblastic leukemia (AMKL), characterized by expression of truncated GATA1 transcription factor protein (GATA1s) due to somatic mutation. The treatment outcome for DS-AMKL is more favorable than for AMKL in non-DS patients. To gain insight into gene expression differences in AMKL, we compared 24 DS and 39 non-DS AMKL samples. We found that non-DS-AMKL samples cluster in two groups, characterized by differences in expression of HOX/TALE family members. Both of these groups are distinct from DS-AMKL, independent of chromosome 21 gene expression. To explore alterations of the GATA1 transcriptome, we used cross-species comparison with genes regulated by GATA1 expression in murine erythroid precursors. Genes repressed after GATA1 induction in the murine system, most notably GATA-2, MYC, and KIT, show increased expression in DS-AMKL, suggesting that GATA1s fail to repress this class of genes. Only a subset of genes that are up-regulated upon GATA1 induction in the murine system show increased expression in DS-AMKL, including GATA1 and BACH1, a probable negative regulator of megakaryocytic differentiation located on chromosome 21. Surprisingly, expression of the chromosome 21 gene RUNX1, a known regulator of megakaryopoiesis, was not elevated in DS-AMKL. Our results identify relevant signatures for distinct AMKL entities and provide insight into gene expression changes associated with these related leukemias.
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页码:3339 / 3344
页数:6
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