Molecular detection of a late-appearing BCR-ABL gene in a child with T-cell acute lymphoblastic leukemia.
Approximately 2-5% of children with newly diagnosed acute lymphoblastic leukemia (ALL) have a Philadelphia (Ph) chromosome detectable on cytogenetic analysis, which is associated with a poor prognosis. In rare ALL cases the Ph chromosome may appear in leukemic cells during the course of the disease. We report here the case of a 5.5-year-old male patient with T-ALL who was found to have the b2a2 BCR-ABL mRNA transcript by reverse transcriptase-polymerase chain reaction (RT-PCR) at first marrow relapse. At the time of initial diagnosis, no BCR-ABL transcripts had been detected by PCR in the patient's blood and marrow samples. Further studies were performed using a competitive PCR titration assay and the fluorescence in situ hybridization (FISH) method to monitor the leukemic clone. Progression of the disease was associated with a higher BCR-ABL transcript level and an increasing proportion of BCR-ABL-positive cells. Metaphase FISH analysis identified the presence of the BCR-ABL fusion gene on a normal chromosome 22. This study shows that a late-appearing Ph translocation in ALL may be cytogenetically invisible. Quantitative RT-PCR and FISH techniques are appropriate and efficient methods for detecting these rare ALL variants expressing the BCR-ABL fusion gene and for estimating the level of residual disease following treatment.
Tchirkov
A
A
Laboratoire de Cytogénétique Médicale, Faculté de Médecine, Clermont-Ferrand, France.
Bons
J M
JM
Chassagne
J
J
Schoepfer
C
C
Kanold
J
J
Briançon
G
G
Giollant
M
M
Malet
P
P
Deméocq
F
F
D002648:Child; D003582:Cytogenetics; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D052138:Genes, Neoplasm; D006801:Humans; D007621:Karyotyping; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D008297:Male
D016044:Fusion Proteins, bcr-abl