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 (also known as
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 suggested 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 (Alpár 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).
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 P202-C1 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.mrcholland.com) and the identity of the genes detected by the reference probes is available in Table 3 of the Product Description.
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