RT/PCR detection of SIL-TAL-1 fusion mRNA in Chinese T-cell acute lymphoblastic leukemia (T-ALL).
The TAL-1 gene is located on chromosome 1p32. In about 20% of T-cell acute lymphoblastic leukemias (T-ALL), this gene is disrupted in its 5' portion by a site-specific 100-kg deletion and is fused with the 5' part of the SIL gene, to form SIL-TAL-1 chimeric gene. In this study, we established a "nested" retrotranscriptase/polymerase chain reaction (RT/PCR) technique which allows detection of the SIL-TAL-1 transcriptional expression. A chimeric mRNA was observed in four of 17 T-ALL cases and has been shown to result from the fusion between the exon 1 of SIL and exon 3 of TAL. A sensitivity test showed that this RT/PCR procedure could detect one leukemic cell among 10(6) normal cells. A positive RT/PCR result was obtained in two cases during clinical remission, suggesting the presence of minimal residual disease (MRD). One patient developed clinical relapse 3 months after PCR positivity. Moreover, analysis of the Tald rearrangement by DNA-based PCR in four patients with SIL-TAL-1 fusion revealed the type A (Tald1) rearrangement in all cases. Sequence analysis demonstrated the presence of N region and non-random "P" nucleotide, as well as base deletions at the genomic SIL-TAL-1 joining site. These data indicate that detection of TAL-1 gene abnormality is important for diagnosis and monitoring of MRD in a subset of T-ALL.
Huang
W
W
Shanghai Institute of Hematology, Rui-Jin Hospital, Samuel Waxman Cancer Research Foundation, China.
Kuang
S Q
SQ
Huang
Q H
QH
Dong
S
S
Zhang
T
T
Gu
L J
LJ
Ching
L M
LM
Chen
S J
SJ
Chang
L C
LC
Chen
Z
Z
D000293:Adolescent; D000328:Adult; D044466:Asian People; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement / Q000235:genetics; D006801:Humans; D016130:Immunophenotyping; D047908:Intracellular Signaling Peptides and Proteins; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015514:Oncogene Proteins, Fusion; D016133:Polymerase Chain Reaction / Q000379:methods*; D011506:Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000032:analysis*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D015514:Oncogene Proteins, Fusion; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C071236:STIL protein, human; C067143:TAL1 protein, human