MHH-TALL1, a T-ALL Cell Line Expressing a Novel BCR-ABL Transcript.

The Philadelphia chromosome (Ph) is the result of the chromosomal translocation t(9;22)(q34;q11), leading to the BCR-ABL fusion gene. The Ph chromosome is the hallmark of chronic myeloid leukemia, but is also detected in acute lymphoblastic leukemia (ALL), particularly in adults. The majority of Ph-positive ALL cases belong to the category of B-cell precursor ALL, whereas Ph-positive T-ALL cases are rather rare. The MHH-TALL1 cell line was established from the peripheral blood of an 11-year-old boy with T-ALL in 1993. PCR analysis of primary tumor cells failed to reveal the existence of a BCR-ABL fusion. Interestingly however, conventional cytogenetics and fluorescence in situ hybridization performed on the cell line showed a 3-way t(1;9;22)(q32;q34;q11) rearrangement effecting Ph formation. As with the patient, standard RT-PCR of the various known BCR-ABL fusion transcripts was negative in the cell line. However, a weak band, about 600 bp larger than the usual e1-a2 BCR-ABL transcript was detected, and subsequently confirmed on reanalysis after optimizing PCR conditions. Sequencing of the RT-PCR product showed that MHH-TALL1 expressed an e6-a2 BCR-ABL fusion transcript. Northern and Western blot analyses demonstrated that the BCR-ABL gene products were expressed at very low levels only. It may be speculated that the presence of this novel BCR-ABL variant has been overlooked in previous analyses, because (i) PCR conditions used to screen for BCR-ABL fusion transcripts were not optimal to detect this variant and (ii) a weak signal running at the “wrong” size might have been neglected. In summary, we report a novel BCR-ABL fusion variant expressed in a T-ALL cell line. Our data raise the intriguing possibility that some BCR-ABL negative cases may express the novel e6-a2 transcript described herein. This might have an impact on treatment of the respective patients with ABL kinase inhibitors.