PMID- 14527352
OWN - NLM
STAT- MEDLINE
DCOM- 20040204
LR  - 20071115
IS  - 0366-6999 (Print)
IS  - 0366-6999 (Linking)
VI  - 116
IP  - 9
DP  - 2003 Sep
TI  - Chromosomal changes detected by fluorescence in situ hybridization in patients 
      with acute lymphoblastic leukemia.
PG  - 1298-303
AB  - OBJECTIVES: To investigate patients with acute lymphoblastic leukemia (ALL) for 
      TEL/AML1 fusion, BCR/ABL fusion, MLL gene rearrangements, and numerical changes 
      of chromosomes 4, 10, 17 and 21 by fluorescence in situ hybridization (FISH) and 
      to determine the relationship and the significance of those findings. METHODS: 
      Fifty-one American patients (34 men and 17 women) were included in this study. Of 
      them there were 41 patients with pro-B cell type ALL, 9 with B cell type ALL and 
      1 with T cell type ALL. Chromosome metaphases of each sample were prepared 
      according to standard protocols. Fluorescence in situ hybridization was performed 
      using commercially available DNA probes, including whole chromosome painting 
      probes, locus specific probes, specific chromosome centromere probes and dual 
      color/multiple color translocation fusion probes. The digital image analysis was 
      carried out using Cytovision and Quips FISH programs. RESULTS: An overall 
      incidence of chromosomal anomalies, including t (9;22), MLL gene rearrangements, 
      t (12;21), and numerical chromosomal anomalies of chromosomes 4, 10, 17 and 21 
      was found in 33 patients (65%). Thirty-one of them were pediatric patients and 
      two adults. The t (12;21) was the commonest chromosomal anomaly detected in this 
      population; 14 out of the 45 pediatric patients (31%) were positive for TEL/AML1 
      fusion, among which three had an additional derivative 21 [t (12;21)], four had a 
      deletion of 12p and two had an extra copy of chromosome 21. All 14 patients with 
      positive TEL/AML1 fusion had ALL pre-B cell or B-cell lineage according to 
      standard immunotyping. The percentage of cells with fusion signals ranged from 
      20% to 80%. All fourteen patients positive for TEL/AML1 gene fusion were mosaic. 
      Three out of the 14 patients positive for the TEL/AML1 gene fusion were 
      originally reported to be culture failures and none of the remaining eleven 
      samples had been found to have chromosome 12 abnormalities by conventional 
      cytogenetic techniques. All pediatric patients with pre-T or T cell lineage and 
      the six adults were negative for TEL/AML1 fusion. One patient had double 
      Philadelphia chromosomes, three had a rearrangement or a deletion of the MLL 
      gene, one had t (4;11) and two had a deletion of the MLL. One of the patients 
      with an MLL deletion also had a large ring of chromosome 21, and r (21) was 
      caused by AML1 gene tandemly duplicated at least five times. The second case with 
      the MLL deletion was also unique, the patient had a t (12;21) as well. A total of 
      20 patients had numerical changes (gain or loss) of chromosomes 4, 10, 17 and 21. 
      Eight patients were found to have trisomies of three or four different 
      chromosomes. Interestingly, seven of these patients did not have TEL/AML1, 
      BCR/ABL or the MLL gene rearrangement; one did have the TEL/AML1 gene fusion. 
      Eleven patients with pro-B cell or B cell type ALL (9 children with ALL, 2 adults 
      with ALL) had numerical changes of chromosome 21 (gain 1 or 2 chromosome 21), 
      among them, 10 patients had no structural alteration of chromosome 21, and one 
      was combined by t (12; 21). Four patients had a monosomy of chromosome 17 and 
      three out of these patients with monosomy 17 also had a fusion signal of 
      TEL/AML1. CONCLUSIONS: FISH plays an important role in detecting chromosome 
      changes, especially in some cryptic chromosome translocations and patients with 
      culture failures. This study found a trend towards a division between patients 
      who had structural changes such as t (12;21) or a ring chromosome 21 and those 
      who had numerical changes of chromosome 21 as well as the patients with TEL/AML1 
      fusion and patients with the coexistence of numerical chromosomal changes of 
      chromosomes 4, 10 and 17. In our opinion there are two separate mechanisms which 
      lead to the development or progression of leukemia.
FAU - Zhang, Lijun
AU  - Zhang L
AD  - Department of Pediatrics, University of Oklahoma, Health Sciences Center, 73104, 
      USA.
FAU - Parkhurst, J B
AU  - Parkhurst JB
FAU - Kern, W F
AU  - Kern WF
FAU - Scott, K V
AU  - Scott KV
FAU - Niccum, D
AU  - Niccum D
FAU - Mulvihill, J J
AU  - Mulvihill JJ
FAU - Li, Shibo
AU  - Li S
LA  - eng
PT  - Journal Article
PL  - China
TA  - Chin Med J (Engl)
JT  - Chinese medical journal
JID - 7513795
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Artificial Gene Fusion
MH  - Child
MH  - Child, Preschool
MH  - *Chromosome Aberrations
MH  - Chromosomes, Human, Pair 10
MH  - Chromosomes, Human, Pair 17
MH  - Chromosomes, Human, Pair 21
MH  - Chromosomes, Human, Pair 4
MH  - Female
MH  - Gene Rearrangement
MH  - Humans
MH  - *In Situ Hybridization, Fluorescence
MH  - Infant
MH  - Male
MH  - Middle Aged
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*genetics
EDAT- 2003/10/07 05:00
MHDA- 2004/02/05 05:00
CRDT- 2003/10/07 05:00
PHST- 2003/10/07 05:00 [pubmed]
PHST- 2004/02/05 05:00 [medline]
PHST- 2003/10/07 05:00 [entrez]
PST - ppublish
SO  - Chin Med J (Engl). 2003 Sep;116(9):1298-303.