PML-RARa

• About this biomarker
• Introduction to our products
• Why choose our products
• Main products for PML-RARa
• Associated products
• Related publications

PML-RARa fusion gene transcripts are the result of the balanced reciprocal translocation (15;17)(q22;q21). This leads to the fusion of the promyelocytic leukemia (PML) gene with the retinoic acid receptor alpha (RARa) to generate the PML-RARa fusion protein, a transcriptional repressor. PML-RARa expression is associated with impaired myeloid differentiation.

Depending on the location of breakpoints within the PML site (intron 6, exon 6 and intron 3) the respective PML RARa transcript subtypes referred to as long (L or bcr1), variant (V or bcr2) and short (S or bcr3), may be formed. They represent 55%, 5% and 40% of the cases respectively. RARa breakpoints always occur in intron 2. The use of all trans retinoic acid (ATRA) and arsenic trioxide ( ATO) has led to dramatic improvements in the outcomes for patients with Acute Promyelocytic Leukemia (APL).

The European LeukemiaNet has developed guidelines for monitoring patients for potential relapse by measuring transcript levels from PML-RARa fusion genes [Sanz MA et al. Blood. 2009]. A recently published prospective trial has demonstrated that sequential quantitative RQ-PCR monitoring of PML-RARa transcripts provided the strongest predictor of relapse free survival in APL patients [Grimwade D et al. JCO. 2009]. IPSOGEN plasmid standards were utilized in this study to establish normalized copy number (NCN) for the transcript levels.

Quantification of PML-RARa copy number by well established standardized RQ-PCR protocol using EAC technology [Gabert J et al. Leukemia. 2003, Beillard E et al. Leukemia. 2003] presents several advantages such as being highly sensitive, facilitating assessment of kinetics and being highly reproducible.

PML-RARa FusionQuant® technology uses Real-Time Quantitative PCR technology to quantify specific PML-RARa fusion gene transcripts (bcr1, bcr2 or bcr3) relative to ABL control gene.

Quantification of PML-RARa fusion gene transcripts has been standardized in the EAC (Europe Against Cancer) program, and IPSOGEN FusionQuant® kits use this validated technology.

Why choose PML-RARa FusionQuant ® Kits?

• EAC Standardized RQ-PCR procedures

• Sensitive and accurate quantification of PML-RARA bcr1, bcr2 and bcr3

• 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

Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet.
Blood. 2009
Authors: Sanz MA et al.

Prospective minimal residual disease monitoring to predict relapse of acute promyelocytic leukemia and to direct pre-emptive arsenic trioxide therapy.
JCO. 2009
Authors: Grimwade D et al.

Standardization and quality control studies of 'real-time' quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia - a Europe Against Cancer program.
Leukemia. 2003
Authors: Gabert J et al.

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.
Leukemia. 2003
Authors: Beillard E et al.