PMID- 11726315
OWN - NLM
STAT- MEDLINE
DCOM- 20021002
LR  - 20231213
IS  - 0390-6078 (Print)
IS  - 0390-6078 (Linking)
VI  - 86
IP  - 12
DP  - 2001 Dec
TI  - Fluorescence in situ hybridization study of TEL/AML1 fusion and other 
      abnormalities involving TEL and AML1 genes. Correlation with cytogenetic findings 
      and prognostic value in children with acute lymphocytic leukemia.
PG  - 1245-53
AB  - BACKGROUND AND OBJECTIVES: The TEL/AML1 fusion is the most common genetic 
      abnormality found in childhood acute lymphoblastic leukemias (ALL). Although it 
      is very difficult to identify by conventional cytogenetic techniques it can be 
      readily detected using fluorescence in situ hybridization (FISH). We carried out 
      cytogenetic and FISH studies on 42 children with ALL in order to know the 
      frequency of this translocation in our population, the incidence of TEL and/or 
      AML1 gene alterations, and their correlation with clinical evolution and 
      prognosis. In addition, we performed reverse transcription polymerase chain 
      reaction (RT-PCR) in some cases, confirming the feasibility of FISH techniques in 
      the detection of this translocation. DESIGN AND METHODS: Bone marrow samples were 
      obtained from 42 childhood ALL patients. The copy number of AML1 and TEL genes 
      were studied using fluorescent in situ hybridization with a dual color DNA probe 
      specific for the AML1 and TEL genes. RESULTS: We found a frequency of TEL/AML1 
      fusion of 17% in our sample. Double TEL/AML1 fusion, lack of TEL signal and extra 
      AML1 signals were frequent additional FISH abnormalities. Duplication of a 
      chromosomal complement, deletion of chromosome 12p arm, and polysomies of 
      chromosome 21 are plausible explanations for these additional FISH findings. 
      However, a relatively high proportion of our cases (9.5%) presented specific 
      amplification of AML1. A statistically significant difference in prognosis was 
      found between patients with and without these additional AML1 or TEL FISH 
      alterations (p<0.02), which could be related to the presence of specific 
      karyotypes. INTERPRETATIONS AND CONCLUSIONS: The frequency of TEL/AML1 fusion is 
      similar to that found in other populations (17%). We found that FISH analysis of 
      AML and TEL is related to the evolution of the disease. The absence of 
      alterations in these genes revealed by FISH could be indicative of bad prognosis, 
      while the presence of alterations is related to a good evolution. Our results 
      suggest that interphase FISH analysis to search for alterations in AML and TEL 
      genes could be extremely useful for complementing cytogenetic studies and for 
      providing additional information about the possible outcome of the disease in 
      patients with ALL.
FAU - Martinez-Ramirez, A
AU  - Martinez-Ramirez A
AD  - Dpto. de Genetica Humana, Programa de Patologia Molecular, Centro Nacional de 
      Investigaciones Oncologicas (CNIO), Ctra. Majadahonda-Pozuelo, Km. 2, 28220 
      Majadahonda, Madrid, Spain. angmartinez@cnio.es
FAU - Urioste, M
AU  - Urioste M
FAU - Contra, T
AU  - Contra T
FAU - Cantalejo, A
AU  - Cantalejo A
FAU - Tavares, A
AU  - Tavares A
FAU - Portero, J A
AU  - Portero JA
FAU - Lopez-Ibor, B
AU  - Lopez-Ibor B
FAU - Bernacer, M
AU  - Bernacer M
FAU - Soto, C
AU  - Soto C
FAU - Cigudosa, J C
AU  - Cigudosa JC
FAU - Benitez, J
AU  - Benitez J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Italy
TA  - Haematologica
JT  - Haematologica
JID - 0417435
RN  - 0 (Core Binding Factor Alpha 2 Subunit)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-ets)
RN  - 0 (RUNX1 protein, human)
RN  - 0 (Repressor Proteins)
RN  - 0 (TEL-AML1 fusion protein)
RN  - 0 (Transcription Factors)
SB  - IM
CIN - Haematologica. 2001 Dec;86(12):1233. PMID: 11726312
MH  - Adolescent
MH  - Bone Marrow
MH  - Child
MH  - Child, Preschool
MH  - Chromosome Aberrations
MH  - Core Binding Factor Alpha 2 Subunit
MH  - Cytogenetic Analysis
MH  - DNA-Binding Proteins/genetics
MH  - Female
MH  - Gene Dosage
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Oncogene Proteins, Fusion/*genetics
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis/*genetics
MH  - Prognosis
MH  - *Proto-Oncogene Proteins
MH  - Proto-Oncogene Proteins c-ets
MH  - Repressor Proteins/genetics
MH  - Transcription Factors/genetics
MH  - ETS Translocation Variant 6 Protein
EDAT- 2001/12/01 10:00
MHDA- 2002/10/03 04:00
CRDT- 2001/12/01 10:00
PHST- 2001/12/01 10:00 [pubmed]
PHST- 2002/10/03 04:00 [medline]
PHST- 2001/12/01 10:00 [entrez]
PST - ppublish
SO  - Haematologica. 2001 Dec;86(12):1245-53.