PMID- 12946992
OWN - NLM
STAT- MEDLINE
DCOM- 20040217
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 103
IP  - 1
DP  - 2004 Jan 1
TI  - Expression analyses identify MLL as a prominent target of 11q23 amplification and 
      support an etiologic role for MLL gain of function in myeloid malignancies.
PG  - 229-35
AB  - MLL amplification was recently recognized as a recurrent aberration in acute 
      myeloid leukemia (AML) and myelodys-plastic syndrome (MDS), associated with 
      adverse prognosis and karyotype complexity. Here we present detailed results of 
      fluorescence in situ hybridization (FISH) and expression analyses of MLL and 5 
      selected 11q candidate oncogenes (CBL, DDX6, ETS1, FLI1, and PLZF) in 31 patient 
      samples and one cell line with 11q23 gain. FISH analyses revealed that the 11q23 
      amplicon invariably encompassed MLL, DDX6, ETS1, and FLI1, whereas expression 
      analyses identified MLL and DDX6 as the most differentially expressed genes among 
      samples with and without 11q23 copy gain or amplification. In MLL-amplified 
      samples, a significant transcriptional up-regulation of MEIS1, PROML1, ADAM10, 
      NKG2D, and ITPA was noted. Further analyses, designed to elucidate a possible 
      role of the 11q overexpressed genes (MLL, DDX6, FLI1, and ETS1) in unselected MDS 
      and AML samples, revealed a significant upregulation of MLL in MDS. Our findings 
      confirm the MLL gene as a prominent target of 11q23 amplification and provide 
      further evidence for an etiologic role for MLL gain of function in myeloid 
      malignancies. In addition, our results indicate that the transcriptional program 
      associated with MLL rearrangements and MLL overexpression displays significant 
      similarities.
FAU - Poppe, Bruce
AU  - Poppe B
AD  - Centre for Medical Genetics, University Hospital Ghent, Belgium.
FAU - Vandesompele, Jo
AU  - Vandesompele J
FAU - Schoch, Claudia
AU  - Schoch C
FAU - Lindvall, Charlotta
AU  - Lindvall C
FAU - Mrozek, Krzysztof
AU  - Mrozek K
FAU - Bloomfield, Clara D
AU  - Bloomfield CD
FAU - Beverloo, H Berna
AU  - Beverloo HB
FAU - Michaux, Lucienne
AU  - Michaux L
FAU - Dastugue, Nicole
AU  - Dastugue N
FAU - Herens, Christian
AU  - Herens C
FAU - Yigit, Nurten
AU  - Yigit N
FAU - De Paepe, Anne
AU  - De Paepe A
FAU - Hagemeijer, Anne
AU  - Hagemeijer A
FAU - Speleman, Frank
AU  - Speleman F
LA  - eng
GR  - P30 CA16058/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030828
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (ETS1 protein, human)
RN  - 0 (FLI1 protein, human)
RN  - 0 (KMT2A protein, human)
RN  - 0 (Proto-Oncogene Protein c-ets-1)
RN  - 0 (Proto-Oncogene Protein c-fli-1)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-ets)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 149025-06-9 (Myeloid-Lymphoid Leukemia Protein)
RN  - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase)
RN  - EC 2.7.7.- (RNA Nucleotidyltransferases)
RN  - EC 3.6.1.- (DDX6 protein, human)
RN  - EC 3.6.4.13 (DEAD-box RNA Helicases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Cell Line, Tumor
MH  - Chromosomes, Human, Pair 11/*genetics
MH  - DEAD-box RNA Helicases
MH  - DNA-Binding Proteins/*genetics
MH  - Female
MH  - Gene Amplification
MH  - Gene Rearrangement
MH  - Histone-Lysine N-Methyltransferase
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Leukemia, Myeloid, Acute/*genetics
MH  - Male
MH  - Middle Aged
MH  - Myelodysplastic Syndromes/*genetics
MH  - Myeloid-Lymphoid Leukemia Protein
MH  - Proto-Oncogene Protein c-ets-1
MH  - Proto-Oncogene Protein c-fli-1
MH  - Proto-Oncogene Proteins/genetics
MH  - Proto-Oncogene Proteins c-ets
MH  - *Proto-Oncogenes
MH  - RNA Nucleotidyltransferases/genetics
MH  - Trans-Activators/genetics
MH  - Transcription Factors/genetics
MH  - Up-Regulation
EDAT- 2003/08/30 05:00
MHDA- 2004/02/18 05:00
CRDT- 2003/08/30 05:00
PHST- 2003/08/30 05:00 [pubmed]
PHST- 2004/02/18 05:00 [medline]
PHST- 2003/08/30 05:00 [entrez]
AID - S0006-4971(20)50309-1 [pii]
AID - 10.1182/blood-2003-06-2163 [doi]
PST - ppublish
SO  - Blood. 2004 Jan 1;103(1):229-35. doi: 10.1182/blood-2003-06-2163. Epub 2003 Aug 
      28.