ACUTE LYMPHOBLASTIC LEUKEMIA
Partial or complete deletions of the IKZF1 (IKAROS) gene (7p12.2) have been detected in acute lymphoblastic leukaemia (ALL) cases, especially in cases that also carried the BCR-ABL1 gene fusion (Philadelphia chromosome). In ALL, IKZF1 deletions have been associated with relapse and very poor clinical outcome in several studies. The P202-B1 probemix contains two probes for each exon of the IKZF1 gene. In addition, it contains three probes for both the IKZF2 (HELIOS, at 2q34) and the IKZF3 (AIOLOS, at 17q21.1) genes, which belong to Ikaros gene family of transcription factors and which have also important roles in the control of mature B-lymphocyte differentiation and proliferation. Four probes target 9p21.3 chromosomal location (CDKN2A-CDKN2B-MIR31 genes), which is often deleted in ALL samples and is associated with poor survival. This mix includes also four probes targeting 14q32.33 chromosomal region. Information on the 14q32 copy number status can be useful for the interpretation of MRD (minimal residual disease) detection using Ig heavy chain rearrangements. Finally, 12 reference probes have been included targeting chromosomal regions that are relatively quiet in ALL. Partial or complete gene deletions of the transcription factor IKZF1 have been detected in 76 % of paediatric and 63-91 % of adult BCR-ABL1 positive ALL cases. In contrast, IKZF1 copy number changes are rare in chronic-phase CML. However, in CML-blast crisis, deletions of IKZF1 are more frequent (25-66 %) and thereby seem to have a role in CML transformation from chronic phase to blast crisis. Partial gene deletion of IKZF1 frequently affect exons 4-7, but even smaller microdeletions, affecting a single exon, have also been reported.