t(9;22) bcr-abl

The bcr-abl rearrangement t(9;22) can be found in 95% of all cases of chronic myeloid leukemia (CML), the most frequent leukemic disease in adults as well in 25% of acute lymphoblastic leukemia (ALL) cases. The rearrangement generates a fusion transcript from the breakpoint cluster region (bcr) and the Abelson leukemia (abl1) gene, resulting in a soluble and non-regulated tyrosine kinase, transforming normal cells to neoplastic CML-cells thus causing an unlimited propagation of white blood cells. The most frequent fusion transcripts are b3a2 and b2a2 (major breakpoint region, M-bcr) and e1a2 (minor breakpoint region, m-bcr) which cover more than 95 % of the t(9;22) fusion transcripts; while fusion transcripts with abl1 exon a3 are rare.1

Besides chromosomal analysis by FISH the most common diagnosis is based on reverse transcription Real-Time-PCR detection of the fusion transcript. The LightCycler®based test from Emig et al. 2 has been used in routine for many years.

In the initial disease diagnosis the amount of the fusion transcript is very high. During therapy with tyrosine kinase inhibitors (Glivec) or after bone marrow transplantation the expression of the fusion transcript is not longer detectable or reduced to very low levels (minimal residual disease MRD), requiring a sensitive detection method and quantification to recognize a relapse. The quantification is normalized against a reference gene; the formerly used glucose-6-phophatedehydrogenase G6PDH 3 (available as LightMix® Kit 40-0137-16) has been replaced in many places by Abl1 (LightMix® Kit 40-0357-16).

1 BCR first exon sequences activate the bcr/abl tyrosine kinase oncogene of Philadelphia chromosome positive human leukemia. Muller AJ, Young JC, Pendergast AM. Molecular Cell Biology 11:1785-1792(1991).

2 Accurate and rapid analysis of residual disease in patients with CML using specific fluorescent hybridization probes for real time quantitative RT-PCR. Emig M. et al., Leukemia (1999) 13, 1825-1832

3 Evaluation of candidate control genes for diagnosis and residual disease detection in leukemic patients using ‘real-time’ quantitative reverse-transcriptase polymerase chain reaction (RQ-PCR) – a Europe against cancer program. Beillard et al. Leukemia. 2003 Dec;17(12):2474-86

Carry over to OligoShop