PMID- 11516105
OWN - NLM
STAT- MEDLINE
DCOM- 20010906
LR  - 20231213
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 15
IP  - 9
DP  - 2001 Sep
TI  - Characterization of additional genetic events in childhood acute lymphoblastic 
      leukemia with TEL/AML1 gene fusion: a molecular cytogenetics study.
PG  - 1442-7
AB  - TEL/AML1 gene fusion that results from a cryptic t(12;21) is the most common 
      genetic aberration in childhood B-lineage acute lymphoblastic leukemia (ALL). 
      While the translocation may initiate the leukemic process, critical secondary 
      genetic events are currently believed to be pivotal for leukemogenesis. We 
      investigated 12 cases of childhood ALL with TEL/AML1 gene fusion by fluorescence 
      in situ hybridization (FISH) and comparative genomic hybridization (CGH) and 
      documented additional or secondary genetic changes in seven patients (58%). Three 
      patients showed extra copies of chromosome 21 including a case in which the 
      trisomy 21 (+21) clone was distinct from the one harboring TEL/AML1 gene fusion. 
      Interestingly, one patient without +21 showed amplification of the AML1 gene on 
      chromosome 21q, supporting the contention that AML1 amplification may be an 
      important additional genetic event. Gene expression study by semi-quantitative 
      reverse-transcription polymerase chain reaction (RT-PCR) in two of these four 
      patients showed an increase in AML1 transcripts that paralleled the increase in 
      gene copy number. Deletion of the normal TEL allele was detected in two patients, 
      with one of them showing loss of chromosome 12 together with duplication of the 
      der(12)t(12;21). Finally, one patient showed duplication of the fusion signal. 
      Our findings confirm that additional or secondary genetic changes including AML1 
      amplification are commonly encountered in childhood ALL with TEL/AML1 gene 
      fusion, which are envisaged to play significant roles in disease progression.
FAU - Ma, S K
AU  - Ma SK
AD  - Department of Pathology, The University of Hong Kong, Queen Mary Hospital, 
      People's Republic of China.
FAU - Wan, T S
AU  - Wan TS
FAU - Cheuk, A T
AU  - Cheuk AT
FAU - Fung, L F
AU  - Fung LF
FAU - Chan, G C
AU  - Chan GC
FAU - Chan, S Y
AU  - Chan SY
FAU - Ha, S Y
AU  - Ha SY
FAU - Chan, L C
AU  - Chan LC
LA  - eng
PT  - Journal Article
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Core Binding Factor Alpha 2 Subunit)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-ets)
RN  - 0 (RUNX1 protein, human)
RN  - 0 (Repressor Proteins)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Adolescent
MH  - *Artificial Gene Fusion
MH  - Child
MH  - Child, Preschool
MH  - Cohort Studies
MH  - Core Binding Factor Alpha 2 Subunit
MH  - DNA-Binding Proteins/*genetics
MH  - Down Syndrome/genetics
MH  - Female
MH  - Humans
MH  - Immunophenotyping
MH  - In Situ Hybridization, Fluorescence
MH  - Karyotyping
MH  - Male
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*genetics
MH  - *Proto-Oncogene Proteins
MH  - Proto-Oncogene Proteins c-ets
MH  - *Repressor Proteins
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transcription Factors/*genetics
MH  - ETS Translocation Variant 6 Protein
EDAT- 2001/08/23 10:00
MHDA- 2001/09/08 10:01
CRDT- 2001/08/23 10:00
PHST- 2001/08/23 10:00 [pubmed]
PHST- 2001/09/08 10:01 [medline]
PHST- 2001/08/23 10:00 [entrez]
AID - 10.1038/sj.leu.2402202 [doi]
PST - ppublish
SO  - Leukemia. 2001 Sep;15(9):1442-7. doi: 10.1038/sj.leu.2402202.