Page 216 - Haematologica Vol. 110 - January 2025

LETTER TO THE EDITOR
non-deleted; P=0.008), resulting in an increase of deaths during induction therapy (62.5 % of deleted patients vs. 5.7% of non-deleted; P=0.0002). Such an adverse response and outcome was also observed among patients with DNMT3A/ N/KRAS/MSH2/U2AF1 SNV, collectively defined as variable as the worse outcome genetic profile (WOG), previously described for the same study cohort.1 In fact, six of eight patients with del(5q) had WOG mutations and consequently, patients with both alterations (WOG + del(5q)) exhibited significantly shorter OS compared to those with only WOG mutations (median OS of 0.16 [range, 0.02- not applicable (NA)] vs. 0.81 [range, 0.45-1.75]; P<0.001), emphasizing the deleterious effect of an additional del(5q) in the WOG pa- tient group.
In T-ALL, the prognostic significance of PTEN alterations remains controversial. Our results showed that neither PTEN
A
CNV nor SVN nor CNV plus SNV had an impact on patient outcome (Online Supplementary Table S1), consistent with previous studies.8,9 Thereby, the genetic signature NOTCH1/ FBXW7wt and/or N/KRASmut and/or PTENalt did not have prog- nostic value in our series (data not shown), and, therefore, our results do not validate the genetic score proposed by Trinquand A. et al.10 to stratify adult T-ALL patients. Regarding the clinical impact of pairwise genetic associations, we observed that patients with deletions in CDKN2A/B genes and cortical immunophenotype exhibited a trend for better OS (Table 2). Finally, patients with a complex tumor genome, defined as >14 alterations (14alt), had poorer OS (Table 2) and lower CR rates (68.8% patients with >14alt achieved CR vs. 97.8% of patients with ≤14alt; P=0.002).
Overall, our results suggest that CNV seem to cooperate with specific SNV/indel, delineating recurrent onco-genet-
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