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SALSA MLPA Probemix P202 IKZF1-ERG

Acute lymphoblastic leukemia (ALL); Chronic myeloid leukemia (CML); Common variable immunodeficiency (CVID)

Region: IKZF1 7p12.2; ERG 21q22.2; CDKN2A 9p21.3; CDKN2B 9p21.3; 14q32

General Information: The SALSA MLPA Probemix P202 IKZF1-ERG is a research use only (RUO) assay for the detection of deletions or duplications in the IKZF1 (7p12.2) and ERG (21q22.2) genes, which are frequently altered in acute lymphoblastic leukemia (ALL). In addition, this probemix can be used to detect copy number aberrations of the CDKN2A/2B genes (9p21.3) and the 14q32.33 chromosomal regions, which are frequently altered in ALL.

Partial or complete deletions of the IKZF1 (IKAROS) gene are detected in ALL, especially in cases that also carry the BCR-ABL1 gene fusion (Philadelphia chromosome). In ALL, IKZF1 deletions have been associated with relapse and poor clinical outcome (Mullighan et al. 2009, Martinelli et al. 2009, and Iacobucci et al. 2009). Partial or complete gene deletions of IKZF1 are detected in ~80% of paediatric and 60-90% of adult BCR-ABL1 positive ALL cases. Partial gene deletions of IKZF1 frequently affect exons 4-7, but smaller intragenic deletions, down to single exon deletions, have been reported and have been shown to be associated with unfavourable prognosis in paediatric B-cell precursor (BCP) ALL (Boer et al. 2016).

Short intragenic deletions of ERG have been described in BCP-ALL patients and have been shown to be associated with good outcome and, moreover, ERG deletion is suggested to define a subgroup of superior outcome among patients with IKZF1 deletions (Clappier et al. 2014 and Zaliova et al. 2014).

In chronic-phase chronic myeloid leukemia (CML), IKZF1 copy number changes are rare. However, in CML-blast crisis, deletions of IKZF1 are more frequent (25-66%) and might therefore have a role in CML transformation from chronic phase to blast crisis (Alpar et al. 2012).

In common variable immunodeficiency (CVID) disorder, characterized by late-onset hypogammaglobulinemia and a poor antibody response to infectious and vaccine antigens, families with germline heterozygous IKZF1 deletions have been detected (Kuehn et al. 2016).

Probemix content: The SALSA MLPA Probemix P202 IKZF1-ERG contains 59 MLPA probes with amplification products between 118 and 504 nucleotides (nt). This includes 21 probes for the IKZF1 gene, 13 probes for the ERG gene, three probes for the CDKN2A/2B genes, four probes for the 14q32.33 chromosomal region, and for both IKZF1 and ERG a telomeric and a centromeric flanking probe. In addition, 14 reference probes are included that detect relatively copy number stable regions in acute lymphoblastic leukemia. Complete probe sequences are available online (www.mlpa.com) and the identity of the genes detected by the reference probes is available in Table 2e.

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.mlpa.com.

Order Items

Probemix

Item no.
Description
Technology
Price
P202-025R
SALSA MLPA Probemix P202 IKZF1-ERG – 25 rxn
€ 243.00
P202-050R
SALSA MLPA Probemix P202 IKZF1-ERG – 50 rxn
€ 486.00
P202-100R
SALSA MLPA Probemix P202 IKZF1-ERG – 100 rxn
€ 972.00

Required Reagents

Item no.
Description
Technology
Price
EK1-FAM
SALSA MLPA EK1 reagent kit – 100 rxn – FAM
€ 300.00
EK1-Cy5
SALSA MLPA EK1 reagent kit – 100 rxn – Cy5
€ 300.00
EK5-FAM
SALSA MLPA EK5 reagent kit – 500 rxn – FAM
€ 1380.00
EK5-Cy5
SALSA MLPA EK5 reagent kit – 500 rxn – Cy5
€ 1380.00
EK20-FAM
SALSA MLPA EK20 reagent kit – 2000 rxn – FAM
€ 5295.00

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Improvements

One IL3RA probe and one flanking probe have been removed, and one flanking probe replaced.