t(16;16) Inversion 16

CBFb-MYH11 fusion transcripts are expressed in acute myeloid leukemias of the M4Eo subtype and occur as a result of inversion 16 (p13q22) or t(16;16) chromosomal abnormalities, causing dysfunctional transcription and leukemogenesis. The CBF-MYH11 fusion protein is believed to bind and sequester CBFa, a protein that with CBFb forms a complex absolutely essential for normal hematopoiesis and differentiation.

These leukemias have a relatively favorable response to high-dose chemotherapy and such patients are generally spared allogeneic bone marrow transplantation. Thus, diagnostic detection of CBFb-MYH11 fusion transcripts are essential for therapeutic decisions. Both TaqMan^® and LightCycler^® hybridization probes¹ based Real-Time PCR methods have been published.

The persistence of INV (16) requires a quantification of the fusion gene expression, especially if following a risk-adapted therapy and for MRD (minimal residual disease) monitoring. A reference transcript (housekeeping gene) is used for the normalization; the formerly used glucose-6-phophate dehydrogenase G6PDH ² (available as LightMix^® Kit 40-0137-16) has been replaced in many places by Abl1 (LightMix^® Kit 40-0357-16), following the recommendation of the EU consortium ³.

¹ Quantitative Real time -MYH11LightCycler PCR in AML with inv (16)/t(16;16) showing five different CBF transcripts. Schnittger S, Schoch C, Mellert G, Landt O, Hiddemann W, Haferlach T. Poster.

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

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