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Deep sequencing method for MRD monitoring in AML
Reported variants associated with CHIP are frequently located in DNMT3A, TET2 or ASXL1 genes, and are detected in the preleukemic phase and during complete AML remission.20-23 Indeed, any gene could carry both CHIP and non-CHIP variants, and these should be evalu- ated for each patient. Moreover, studies have shown that genes related to CHIP (IDH1/2) are useful for predicting
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prognosis because in these cases the genetic alterations have been acquired in the leukemic clone and not before.24 The sensitivity of this method equates to one mutated cell per 100,000 cells (LOQ 10-5) for NPM1 and one mutat- ed cell per 10,000 cells (LOQ 10-4) for IDH1, IDH2 and FLT3-SNV. This difference in sensitivity is related to the fact that the NPM1 type A mutation (insCCTG) is rarely
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EF
Figure 3. Analysis of overall sur- vival and disease-free survival in patients with acute myeloid leukemia stratified according to minimal residual disease lev- els determined by sequencing. Analysis of overall survival for (A) the induction data set, (C) the consolidation data set, and (C) both together. Analysis of disease-free survival for (B) the induction data set, (D) the con- solidation data set, and (F) both together. The cutoff used for overall and disease-free survival was 0.001 at the post–induc- tion check-point (n=35), 0.00026 at the post-consolida- tion check–point (n=28) and 0.00035 for both check-points (all data set) (n=63). The num- bers of censored patients with respect to the stratified groups and the numbers at risk are indicated. Statistically signifi- cant values: *P<0.05, **P<0.01.
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