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AML genomes tend to be less mutated compared to other cancers. Nevertheless, a number of mutations in AML cells involve genes which are implicated in epigenetic changes affecting gene activity and expression.1 Broadly, epigenetic functions that become dysregulated include: DNA methylation, DNA hydroxymethylation, histone acetylation, histone lysine methylation, and other histone modifications. Examples for epigenetic modifier gene mutations are DNMT3A, ETO, TET1/2, IDH1/2 and ASXL1. As epigenetic changes do not result in changes to the DNA sequence, they can be modified to some extent by targeted drug intervention.
Qingyu Xu, Department of Hematology and BMT Center, Chinese PLA General Hospital, Beijing, CN, and colleagues, aimed to look at treatment with a hypomethylating agent, decitabine, and whether epigenetic changes predict response. They studied patients with intermediate risk AML (IR-AML) as they had noted that patients frequently have epigenetic modifier gene mutations (EMMs) such as DNMT3A, TET1/2, IDH1/2 and ASXL1.2 They aimed to assess how IR-AML patients (n=83) responded to the addition of hypomethylating agent (HMA) decitabine, to CAG (cytarabine, aclarubicin and granulocyte colony-stimulating factor; G-CSF) induction therapy (DCAG).
All patients | DCAG regimen | “7+3” Standard induction regimens | ||
---|---|---|---|---|
EMM (+) | EMM (-) | EMM (+) | EMM (-) | |
Gender (%) | ||||
Female | 10 (58.8) | 12 (66.7) | 11 (55) | 14 (50) |
Male | 7 (41.2) | 6 (33.3) | 9 (45) | 14 (50) |
Total | 17 | 18 | 20 | 28 |
Median age, year (range) | 59 (46–73) | 56 (14–74) | 45.5 (20–64) | 35.5 (15–61) |
Table 2. Multivariate analysis
Abbreviations: 95% CI, 95% confidence interval; CR, complete remission; DCAG, decitabine with cytarabine, aclarubicin and granulocyte colony-stimulating factor; EFS, event-free survival; EMM (−), epigenetic modifier gene mutations-negative; EMM (+), epigenetic modifier gene mutations-positive; HR, hazard risk; ORR, overall response rate (complete remission rate + partial remission rate); OS, overall survival; RFS, relapse-free survival; RR, relative risk. | ||||
Outcomes | DCAG vs Standard induction | EMM (+) vs EMM (-) | ||
---|---|---|---|---|
EMM (+) [RR/HR, 95% CI (p)] |
EMM (−) [RR/HR, 95% CI (p)] |
DCAG regimen [RR/HR, 95% CI (p)] |
Standard induction regimens [RR/HR, 95% CI (p)] |
|
OS | 0.12, 0.02–1.71 (0.02) | 2.56, 0.60–10.88 (0.20) | 0.10, 0.01–0.97 (0.047) | 6.93, 1.19–40.34 (0.03) |
EFS | 0.05, 0.01–0.34 (0.002) | 0.62, 0.16–2.50 (0.51) | 0.16, 0.03–0.90 (0.04) | 7.01, 1.40–35.15 (0.02) |
RFS | 0.02, 0.002–0.41 (0.01) | 0.40, 0.06–2.82 (0.36) | 0.06, 0.003–1.12 (0.06) | 12.39, 1.13–135.85 (0.04) |
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