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 lymphoblasti c leukemia (ALL) have a Philadelphia (Ph) chromosome detectable on cyt ogenetic analysis, which is associated with a poor prognosis. In rare ALL cases the Ph chromosome may appear in leukemic cells during the co urse of the disease. We report here the case of a 5.5-year-old male pa tient with T-ALL who was found to have the b2a2 BCR-ABL mRNA transcrip t by reverse transcriptase-polymerase chain reaction (RT-PCR) at first marrow relapse. At the time of initial diagnosis, no BCR-ABL transcri pts had been detected by PCR in the patient's blood and marrow samples . Further studies were performed using a competitive PCR titration ass ay 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-AB L-positive cells. Meta phase FISH analysis identified the presence of the BCR-ABL fusion gene on a normal chromosome 22. This study shows th at a late-appearing Ph translocation in ALL may be cytogenetically inv isible. Quantitative RT-PCR and FISH techniques are appropriate and ef ficient methods for detecting these rare ALL variants expressing the B CR-ABL fusion gene and for estimating the level of residual disease fo llowing treatment.