Table 2.
Incidence and prognosis of DNMT3A and IDH1/2 mutations in AML, MDS and myeloproliferative neoplasms
| Study | DNMT3A | IDH1 | IDH2 | Association of mutation with prognosis | Reference |
|---|---|---|---|---|---|
| AML | |||||
| Mardis et al. (n =80) | ND | 16% in NC | ND | IDH1: no association with OS; possible worse OS in AML with NC and wild-type NPM1 | 55 |
| Marcucci et al. (n =358) | ND | 14% | 19% | IDH1: worse DFS IDH2 (R172): lower CR |
49 |
| Wagner et al. (n =275) | ND | R132: 10.9% | ND | IDH1 R132: no association with prognosis NPM1/mutated FLT3 |
52 |
| Paschka et al. (n =805) | ND | 7.6% | 8.7% | IDH1/2: worse RFS and OS in NC with mutated NPM1/wild-type FLT3 | 50 |
| Abbas et al. (n =893) | ND | 6% | 11% | IDH1/2: worse OS in NC with wild-type NPM1/wild-type FLT3 |
47 |
| Caramazza et al. (n =26) | ND | IDH1/2: 19% in AML with trisomy 8 | IDH1/2: 19% in AML with trisomy 8 | ND | 53 |
| Figueroa et al. (n =385) | ND | 6.2% | 8.6% (IDH1/2: 27.1% in NC) | ND | 25 |
| Ley et al. (n =281) | 22.1% (33.7% in NC) | ND | ND | DNMT3A: worse OS | 16 |
| Patel et al. (n =199) | ND | 6% | 2% (IDH1/2: 11.8% in NC) | ND | 56 |
| Chou et al. (n =446) | ND | 6.1% | 12.1% | IDH1: no association with prognosis IDH2: better prognosis, but worse OS in mutated FLT3 |
27 |
| Yan et al. (n =112) | 20.5% | ND | ND | DNMT3A: worse IS, time to treatment failure and lower CR | 18 |
| Thol et al. (n =489) | 17.8% | ND | ND | DNMT3A: worse OS overall; worse OS and CR in NC; worse OS, RFS and lower CR in NC with wild-type NPM1/wild-type FLT3 |
20 |
| Shen et al. (n =605) | 12.3% | 9.3% | 9.8% | DNMT3A: worse OS, EFS and lower CR IDH1/2: no association with prognosis |
36 |
| Hou et al. (n =500) | 14% (22.9% in NC) | ND | ND | DNMT3A: worse OS and RFS | 39 |
| Markova et al. (n =226) | 29.6% in NC | ND | ND | DNMT3A: higher relapse rate, especially in mutated FLT3 | 41 |
| Chotirat et al. (n =230) | ND | 8.7% | 10.4% | IDH1/2: no association with prognosis | 54 |
| Marcucci et al. (n =415) | 35.3% in age<60; 33.3% in age≥60 | ND | ND | DNMT3A: worse DFS, trend toward worse OS Younger patients with non-R882 mutations: worse DFS and OS Older patients with R882 mutations: shorter DFS and OS |
21 |
| Patel et al. (n =398) | 23% | 7% | 8% | DNMT3A: worse OS in mutated FLT3; predictive of response to high-dose daunorubicin IDH1/2: better OS in mutated NPM1 IDH2: better OS |
43 |
| Ravandi et al. (n =170) | ND | IDH1/2: 30% | IDH1/2: 30% | IDH1/2: no association with prognosis; worse OS in mutated NPM1/wild-type FLT3 | 51 |
| Renneville et al. (n =123) | 29% in NC | ND | ND | DNMT3A: worse OS and EFS | 44 |
| Ribeiro et al. (n =415) | 23.1% | ND | ND | DNMT3A: worse OS and RFS, especially in wild-type NPM1/wild-type FLT3 | 23 |
| Fernandez-Mercado et al. (n =84) | 16.7% in NC | 12.2% in NC | 12.2% in NC | ND | 37 |
| Hájková et al. (n =79) | 41% | ND | ND | ND | 22 |
| Westman et al. (n =11) | ND | IDH1/2: 12% | IDH1/2: 12% | ND | 59 |
| Ostronoff et al. (n =191) | 19% | ND | ND | DNMT3A: worse OS, EFS and RFS | 42 |
| Koszarska et al. (n =376) | ND | 8.5% | 7.5% | IDH1/2: no association with prognosis IDH1 R132H: worse OS |
48 |
| The Cancer Genome Atlas Research Network (n =200) | 26% | IDH1/2: 20% | IDH1/2: 20% | ND | 11 |
| Gaidzik et al. (n =1770) | 20.9% | ND | ND | DNMT3A: no association with prognosis R882: worse RFS non-R882: better OS |
38 |
| Roller et al. (n =194) | 41% in NC | ND | ND | ND | 45 |
| Hou et al. (n =318) | 14.9% (19.5% in NC) | ND | ND | DNMT3A: worse OS and EFS | 40 |
| Haferlach et al. (n =1291) | 30.9% | 8.8% | 16.4% | ND | 46 |
| MDS | |||||
| Kosmider et al. (n =100) | ND | 2% | 3% | IDH1/2: no impact on survival | 69 |
| Patnaik et al. (n =88) | ND | 0% | 0% | ND | 72 |
| Rocquain et al. (n =65) | ND | 3% | 5% | ND | 102 |
| Thol et al. (n =193) | ND | 4% | 0% | IDH1: associated with inferior OS and higher rate of transformation to AML | 71 |
| Ewalt et al. (n =100) | 5% | ND | ND | ND | 66 |
| Brecqueville et al. (n =66) | 6% | IDH1/2: 5% | IDH1/2: 5% | ND | 65 |
| Walter et al. (n =150) | 8.7% | ND | ND | DNMT3A: worse OS and increased progression to AML | 68 |
| Lin et al. (n =51) | 7.8% | ND | ND | DNMT3A: worse OS | 64 |
| Thol et al. (n =193) | 2.6% | ND | ND | DNMT3A: increased progression to AML | 67 |
| Patnaik et al. (n =277) | ND | 3% | 9% | IDH1: associated with inferior survival | 70 |
| Roller et al. (n =115) | 13% | ND | ND | DNMT3A: no impact on survival | 45 |
| Myeloproliferative Neoplasms | |||||
| Green et al. (n =180) | ND | 0% | 0% | ND | 77 |
| Kosmider et al. (n =100 CMML) | ND | 0% | 8% | IDH1/2: no impact on survival | 69 |
| Pardanani et al. (n =166) | ND | IDH1/2: 3% | IDH1/2: 3% | ND | 78 |
| Tefferi et al. (n =1422) | ND | 1% | 1% | IDH1/2: no impact on survival in 111 patients with primary myelofibrosis | 80 |
| Brecqueville et al. (n =135) | 1% | 0% | 0% | ND | 65 |
| Abdel-Wahab et al. (n =68 MPN; 15 CMML) | 4% (MPN) 0% (CMML) |
ND | ND | DNMT3A: no patients underwent leukemic transformation in follow-up time | 74 |
| Stegelmann et al. (n =80) | 5% | ND | ND | ND | 76 |
| Jankowski et al. (n =52 CMML) | 4% | ND | ND | DNMT3A: no impact on survival | 75 |
| Tefferi et al. (n =130 PMF) | ND | 4% | 5% | IDH1/2: inferior OS and LFS, more pronounced in presence of JAK2V617F | 79 |
| Vannucchi et al. (n =879 PMF) | 5.7% | IDH1/2: 2.6% | IDH1/2: 2.6% | IDH1/2: inferior LFS | 81 |
Abbreviations: AML, acute myeloid leukemia; CMML, chronic myelomonocytic leukemia; CR, complete remission; DFS, disease-free survival; EFS, event-free survival; LFS, leukemia-free survival; MDS, myelodysplastic syndrome; MPN, myeloproliferative neoplasms; NC, normal cytogenetics; ND, not determined; OS, overall survival; PMF, primary myelofibrosis; RFS, relapse-free survival.