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Additional genomic lesions in adult Ph+ ALL
cantly better DFS (64.3% versus 32.1%; P=0.031) (Figure 4A) and overall survival (77.9% versus 48.4%; P=0.036) (Figure 4B).
Prognostic impact of known and novel genomic lesions in univariate and multivariate analyses
Lastly, ΔKRAS was more frequently found in patients who obtained a CMR (24% versus 3%; P=0.009), but this finding did not have an impact on DFS.
In univariate analysis, ΔMEF2C-long and ΔKRAS had an impact on CMR achievement, while ΔMEF2C-long and ΔIKZF1+CDKN2A and/or PAX5 influenced DFS (Table 3).
In multivariate analysis for CMR, performed taking into
AB
Figure 2. Representation of ΔMEF2C and ΔKRAS. (A) Representation of ΔMEF2C for each patient. Lesions are ordered according to their size: one case had a dele- tion of the whole gene, one had a deletion that involved only exon 1 spanning from intron 1-2 to the 5’ untranslated region (5’UTR), four had deletions starting from intron 2-3 and ending at 5’-UTR, thereby involving both exons 2 and 1 (the latter being an untranslated exon), 13 had lesions spanning from intron 2-3 to intron 1- 2, therefore involving exon 2 (the first codifying exon), with six of them harboring a longer intron 1-2 deletion. Lastly, two cases had deletions that involved only intron 1-2. The first 14 cases were considered as ΔMEF2C-long and the remaining as ΔMEF2C-short. (B) Representation of ΔKRAS for each patient. Lesions are ordered according to their size: in four cases, the deletion encompassed only KRAS itself, whereas in three it involved the short arm of chromosome 12. INTR: intron; EX: exon; 5’UTR: 5’ untranslated region.
AB
CD
Figure 3. Survival probability curves according to IKZF1 status. (A) Disease-free survival and (B) overall survival at 36 months of patients divided according to IKZF1 isoform. (C) Disease-free survival and (D) overall survival at 36 months of ΔIKZF1-only and ΔIKZF1+ CDKN2A and/or PAX5 patients. WT: wild-type; DFS: disease-free survival; OS: overall survival; CR: complete remission.
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