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The distribution of genetic mutations affects seven out of 20 patients (35%), mainly related to I TP53 i (six patients, 30%), I TET2 i (two patients, 10%) and I DNMT3A i (two patients, 10%). During the long-term follow-ups of randomized controlled trials (RCTs), some cases of therapy-associated myeloid neoplasms (t-MNs), including myelodysplastic syndrome (t-MDS) and acute myeloid leukaemia (t-AML), were reported both in the poly(ADP-ribose)polymerase inhibitors (PARPi) and control arms. For the 21 patients, t-MNs occurred after a median latency period of 18-2 (IQR 10-0-30-0) months following first PARPi exposure. Among them, 113 out of 32 662 patients (0-3%) with OC experienced t-MNs after a mean time from first primary cancer diagnosis of 5-3 years for t-MDS ( I n i = 47 patients) and 4-5 years for t-AML ( I n i = 66 patients), with an overall standardized incidence ratio of 5-8 (4-8-6-9).8 Our shorter latency may be linked to an underlying clonal haematopoiesis as I TET2 i and I DNMT3A i mutations were frequently found. [Extracted from the article]

Nine of 13 (70%) MLPA-detected ex1 samples displayed exon 1 levels at half those of healthy donors, similar to samples with single I IKZF1 i copies. Both alleles were mutated (a complete deletion and a 5' deletion) in Patient 6; here, IKAROS expression was completely lost in most cells, though some cells retained intermediate IKAROS levels, suggesting clonal heterogeneity. To determine if the 5' deletions affect mRNA expression, I IKZF1 i mRNA levels from 7 ex1-only patients were compared with those of patients with different I IKZF1 i status (wildtype [WT], mono- and biallelic deletions) by reverse transcription-qPCR, using primers to amplify exons 4-5 (Fig C). One common single nucleotide polymorphism (SNP) (rs61731355; C->A at position Chr7:50,400,069 within exon 8) was detected in the gDNA and mRNA (cDNA) of 2 control patients, showing that I IKZF1 i is biallelically expressed in BCP-ALL cells (Fig D). [Extracted from the article]