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Among the most frequent genomic lesions in Acute Myeloid Leukemia (AML) are the reciprocal translocation t(8;21)(q22q22) and the pericentric inversion of chromosome 16, inv(16) (p13q22). The corresponding leukemia-specific fusion transcripts are respectively AML1-ETO (or RUNX1 RUNX1T1) and CBFβ-MYH11, detected respectively in about 2-12% and 1-5% of AML cases and associated with favorable prognosis.
AML1-ETO (or RUNX1 RUNX1T1) and CBFβ-MYH11 are a clinicopathologic genetic entity that is recognized in the WHO category of AML with recurrent genetic abnormalities.
Because both rearrangements affect the genes for CBF (Core Binding Factor) transcription factor complex, they are also referred to as CBF Leukemias. Patients with these CBF Leukemias are usually younger than 60 years of age. AML1-ETO fusion transcript is often associated with M2 Subtype, whereas patients with CBFβ-MYH11 normally show a myelomonocytic leukemia with abnormal eosinophils.
AML1-ETO and CBFβ-MYH11 need to be accurately identified since they imply relatively good prognosis and therefore enable the use of less toxic interventions compared with other AMLs [Lane S et al. Leukemia & Lymphoma. 2008, Schnittger S et al. Blood. 2003, Grimwade D et al. Best practice and Research Clinical Haematology, 2001].
Moreover, it is generally accepted that in CBF Leukemia patients, a high complete hematologic remission rate can be achieved after a standard induction chemotherapy with cytarabine and anthracycline. However even after such therapies, some patients suffer from relapse, and both rearrangements can be sensitively detected by RQ-PCR, and MRD analysis might give additional information about treatment response [Lane S et al. Leukemia & Lymphoma. 2008, Schnittger S et al. Blood. 2003, Grimwade D et al. Best practice and Research Clinical Haematology, 2001, Krauter J et al. J. Clin. Oncol. (JCO). 2003, Corbacioglu et al. J. Clin. Oncol. (JCO). 2010].
CBFβ-MYH11 FusionQuant® kit uses RQ-PCR technology to detect and quantify the CBFβ-MYH11 translocations (fusion gene transcripts) relative to control gene expression.
Quantification of CBFβ-MYH1 fusion gene transcripts has been standardized in the EAC (Europe Against Cancer) program, and IPSOGEN FusionQuant® kits use this validated technology.
EAC Standardized RQ-PCR procedures
Calibrated and sensitive quantification of fusion gene transcript expression, normalized with ABL control gene expression (results in NCN)
Product manufactured under ISO 13485 certification ensuring optimal quality control and full traceability
A >or=1 log rise in RQ-PCR transcript levels defines molecular relapse in core binding factor acute myeloid leukemia and predicts subsequent morphologic relapse.
Leuk Lymphoma. 2008
Authors: Lane S et al.
New score predicting for prognosis in PML-RARA+, AML1-ETO+, or CBFBMYH11+ acute myeloid leukemia based on quantification of fusion transcripts.
Blood. 2003
Authors: Schnittger S et al.
The clinical significance of cytogenetic abnormalities in acute myeloid leukaemia.
Best practice and Research Clinical Haematology. 2001
Author: Grimwade D.
Prognostic value of minimal residual disease quantification by real-time reverse transcriptase polymerase chain reaction in patients with core binding factor leukemias.
J Clin Oncol. 2003
Authors: Krauter J et al.
Prognostic Impact of Minimal Residual Disease in CBFB-MYH11-Positive Acute Myeloid Leukemia.
J Clin Oncol. 2010
Authors: Corbacioglu A et al.
