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SALSA MLPA Probemix P327 iAMP21-ERG

Acute lymphoblastic leukaemia (ALL); iAMP21

Region: RUNX1 21q22.12; ERG 21q22.2

General information
The SALSA MLPA Probemix P327 iAMP21-ERG is a research use only (RUO) assay for the detection of deletions, duplications or amplifications of specific sequences on chromosome 21, which are associated with acute lymphoblastic leukemia (ALL), myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).

ALL is a heterogeneous disease at the cytogenetic level. This can be utilized in defining clinically significant genetic subgroups to aid in risk stratification and in the treatment selection of ALL. Intrachromosomal amplification of chromosome 21 (iAMP21) is a recurrent chromosomal abnormality detected in ~2% of childhood B-lineage ALL patients (Harrison 2015). iAMP21 is more common in older children and adolescents with ALL (Soulier et al. 2003). Although the level and extent of the amplified region on chromosome 21 seems to vary between ALL patients, the common region of amplification contains the RUNX1 (AML1) gene, at 21q22.12. Clinical studies have shown that ALL patients with iAMP21 have an increased risk of relapse and significantly inferior survival compared to patients without this genetic change (Robinson et al. 2003; Moorman et al. 2010; Harrison 2015). Thereby ALL patients with iAMP21 are suggested to be treated with a more intense regimen (Moorman et al. 2013).

Similar chromosome 21 amplifications have also been reported in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), and are suggested to associate with poor survival (Marcucci et al. 2005; Thol et al. 2012; Weber et al. 2016).
Short intragenic deletions of ERG, at 21q22.12, are also frequently described in B-cell precursor (BCP) ALL patients. BCP-ALL patients with intragenic ERG deletion are suggested to have a favourable clinical outcome and, moreover, ERG deletion is suggested to define a subgroup of superior outcomes among patients with IKZF1 ∆4-7 deletions (Clappier et al. 2014; Zaliova et al. 2014).

This SALSA MLPA probemix is not CE/FDA registered for use in diagnostic procedures. Purchase of this product includes a limited license for research purposes.

Probemix content
The SALSA MLPA Probemix P327-B2 iAMP21-ERG contains 59 MLPA probes with amplification products between 126 and 504 nucleotides (nt). This includes 13 probes for the ERG gene, covering each exon of transcript variants 1-6 and 8, and six probes specific for the RUNX1 gene. Several other probes are located in the regions 21q11.2-q22.3 that are also frequently duplicated, amplified or deleted in iAMP21 cases. In addition, 13 reference probes are included, detecting chromosomal regions that are relatively copy number stable in ALL. Complete probe sequences and the identity of the genes detected by the reference probes are available in Table 3 and online (www.mrcholland.com).

This probemix contains nine quality control fragments generating amplification products between 64 and 105 nt: four DNA Quantity fragments (Q-fragments), two DNA Denaturation fragments (D-fragments), one Benchmark fragment, and one chromosome X and one chromosome Y-specific fragment. More information on how to interpret observations on these control fragments can be found in the MLPA General Protocol and online at www.mrcholland.com.

Order Items

Probemix

Item no.
Description
Technology
Price
P327-025R
SALSA MLPA Probemix P327 iAMP21-ERG – 25 rxn
€ 281.00
P327-050R
SALSA MLPA Probemix P327 iAMP21-ERG – 50 rxn
€ 550.00
P327-100R
SALSA MLPA Probemix P327 iAMP21-ERG – 100 rxn
€ 1075.00

Required Reagents (Sold Separately)

Item no.
Description
Technology
Price
EK1-FAM
SALSA MLPA Reagent Kit – 100 rxn – FAM
€ 341.00
EK1-Cy5
SALSA MLPA Reagent Kit – 100 rxn – Cy5
€ 341.00
EK5-FAM
SALSA MLPA Reagent Kit – 500 rxn – FAM
€ 1571.00
EK5-Cy5
SALSA MLPA Reagent Kit – 500 rxn – Cy5
€ 1571.00
EK20-FAM
SALSA MLPA Reagent Kit – 2000 rxn – FAM
€ 6037.00

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Improvements

One PAX5 specific probe has been replaced.