Table 1.
Prevalence of NPM1 mutations in patients with MDS or MDS/MPN: review of the literature.
| Reference | Type of Study | Number of Cases | Median Age (Range), Years | Sex (M/F) | Molecular Analysis | Overall Frequency of NPM1 Mutations Analyzed in MNs with <20% Blasts | Frequency of NPM1 Mutations in MDS Cases | Frequency of NPM1 Mutations in MDS/MPN Cases | Frequency of NPM1 Mutations in CMML Cases |
|---|---|---|---|---|---|---|---|---|---|
| Caudill et al., 2006 [45] | Monocenter | 90 | NA | NA | PCR | 3/90 (3.3%) | 0/30 | 3/60 (5%) | 3/60 (5%) |
| Oki et al., 2006 [46] | Monocenter, retrospective | 199 * | NA | NA | PCR | 2/115 (1.7%) | 0/50 | 2/65 (3.1%) | 2/50 (4%) |
| Zhang et al., 2007 [47] | Monocenter | 38 | NA | NA | PCR | 2/38 (5.2%) | 2/38 (5.2%) | - | - |
| Shiseki et al., 2007 [48] | Monocenter | 28 ^ | 70 (29–85) § | 17/11§ | PCR | 0/16 | 0/16 | - | - |
| Ishikawa et al., 2008 [49] | Monocenter | 36 | 58 (28–89) | 24/12 | PCR | 2/36 (5.5%) | 2/36 (5.5%) | - | - |
| Andersen et al., 2008 [50] | Monocenter, retrospective | 140 ^ | 61 | 67/73 | PCR | 3/89 (3.4%) ° | 3/89 (3.4%) ° | - | - |
| Bacher et al., 2009 [51] | Monocenter, retrospective | 166 | NA | NA | PCR | 2/166 (1.2%) | 2/149 (1.3%) | 0/17 | 0/17 |
| Chen et al., 2009 [52] | Monocenter, retrospective | 29 | 62 (22–77) | 18/11 | PCR | 0/29 | - | 0/29 | 0/29 |
| Ernst et al., 2010 [53] | Multicenter, retrospective | 187 | NA | NA | PCR | 6/187 (3.2%) | - | 6/187 (3.2%) | 6/97 (6.2%) |
| Rocquain et al., 2010 [54] | Multicenter, retrospective | 129 ^ | NA | NA | NGS/PCR | 0/65 | 0/65 | - | - |
| Li et al., 2010 [55] | - | 232 | NA | NA | PCR | 9/232 (3.9%) | 9/232 (3.9%) | - | - |
| Thol et al., 2010 [56] | Multicenter, retrospective | 193 | 65 (36–92) | 119/74 | PCR | 1/193 (0.5%) | 1/193 (0.5%) | - | - |
| Gritsaev et al., 2010 [57] | - | 44 | NA | NA | PCR | 5/44 (11.4%) | - | - | - |
| Gelsi-Boyer et al., 2010 [58] | Multicenter, prospective | 53 | 71 (41–88) | 36/17 | PCR | 0/49 | - | 0/49 | 0/49 |
| Dicker et al., 2010 [37] | Monocenter | 269 ^ | 69.4 | 120/82 | PCR | 1/73 (1.4%) | 1/66 (1.5%) | 0/7 | 0/7 |
| Bejar et al., 2011 [59] | Multicenter, retrospective | 439 | 70 | 306/133 | NGS | 8/439 (1.8%) | 8/439 (1.8%) | - | - |
| Bacher et al., 2011 [60] | Monocenter, retrospective | 212 ^ | 68.8 (18–88) § | 139/73 § | PCR | 3/34 (8.8%) | 3/34 (8.8%) | - | - |
| Machado-Neto et al., 2011 [61] | Monocenter | 51 ^ | 63 (26–90) § | 30/21§ | PCR | 0/46 | 0/46 | - | - |
| Bains et al., 2011 [62] | Monocenter, retrospective | 160 | 68 (22–89) | 98/62 | PCR | 7/160 (4.4%) | 4/139 (2.9%) | 3/21 (14.3%) | 2/15 (13.3%) |
| Papaemmanuil et al., 2013 [63] | Multicenter | 738 ^ | 68 ± 13 (mean) § | 415/323 § | NGS/WGA | 4/703 (0.6%) | 3/613 (0.5%) | 1/90 (1.1%) | 1/70 (1.4%) |
| Courville et al., 2013 [40] | Retrospective, multicenter | 44 | NA | NA | PCR | 2/44 (4.5%) | - | 2/44 (4.5%) | 2/44 (4.5%) |
| Itzykson et al., 2013 [64] | Multicenter, retrospective | 260 | 74 (41–93) | 210/102 | PCR | 3/260 (1.1%) | - | 3/260 (1.1%) | 3/260 (1.1%) |
| Walter et al., 2013 [65] | Monocenter, retrospective | 157^ | 93 pt (62%) > 60 years | 92/58 | NGS | 4/150 (2.7%) | 4/150 (2.7%) | - | - |
| Wang et al., 2014 [66] | Multicenter, retrospective | 134 | 72 (42–88) § | 89/45§ | PCR | 0/37 | - | 0/37 | - |
| Haferlach et al., 2014 [67] | Multicenter | 944 | 72.8 (23.3–90.8) | 580/364 | NGS | 27/944 (2.9%) | 27/944 (2.9%) | - | - |
| Xu et al., 2014 [68] | Multicenter | 196 | 56 | 109/87 | WGS/PCR | 5/196 (2.6%) | 5/196 (2.6%) | - | - |
| Forghieri et al., 2015 [69] | Monocenter, retrospective | 177 | 77 (47–93) | 109/68 | PCR | 4/135 (3%) | 2/108 (1.9%) | 2/27 (7.4%) | 0/16 |
| Cargo et al., 2015 [70] | Monocenter, retrospective | 69 | NA | NA | PCR/NGS | 3/69 (4.3%) | 3/69 (4.3%) | - | - |
| Peng et al., 2016 [71] | Monocenter, retrospective | 152 | 72 (27–92) | 110/42 | PCR/NGS | 8/152 (5.3%) | - | 8/152 (5.3%) | 8/152 (5.3%) |
| Bartels et al., 2016 [72] | Monocenter, retrospective | 185 * (125) §§ | 72 (14–91) | NA | NGS | 1/81 (1.2%) §§ | 1/47 (2.1%) §§ | 0/44 §§ | 0/34 §§ |
| Reinig et al., 2016 [73] | Monocenter, retrospective | 110 * | 63 (5–83) § | 77/33§ | NGS | 0/53 | 0/39 | 0/14 | 0/14 |
| Makishima et al., 2017 [74] | Multicenter | 699 | NA | NA | NGS | 32/1890 (1.7%) °° | 32/1890 (1.7%) °° | - | - |
| Vallapureddy et al., 2017 [75] | Monocenter, retrospective | 373 | 71 (20–95) | 246/127 | NGS | 8/373 (2%) | - | 8/373 (2%) | 8/373 (2%) |
| Xu et al., 2017 [76] | Monocenter, prospective | 125 | 49 (14–82) | 83/42 | NGS | 2/125 (1.6%) | 2/125 (1.6%) | - | - |
| Idossa et al., 2018 [77] | Monocenter, retrospective | 357 | 74 (28–96) | 250/107 | NGS | NA | NA | NA | NA |
| Hamilton et al., 2018 [78] | Multicenter, retrospective | 80 | 52 (12–70) | 43/37 | NGS | 2/80 (2.5%) | 2/80 (2.5%) | - | - |
| Montalban-Bravo et al., 2019 [79] | Multicenter, retrospective | 1900 | 62 (19–86) ^^ | 13/18^^ | PCR/NGS | 31/1900 (1.6%) | NA | NA | NA |
| Hwang et al., 2019 [80] | Monocenter, retrospective | 35 | 71 (18–85) | 24/11 | NGS | 4/35 (11.4%) | - | 4/35 (11.4%) | 4/35 (11.4%) |
| Zheng et al., 2019 [81] | Monocenter, prospective | 207 *** | 60 (4–91) § | 113/94 § | NGS | 2/115 (1.7%) | 2/115 (1.7%) | - | - |
| Vantyghem et al., 2020 [82] | Multicenter | 177 *** | 60 (10–87) § | 100/77 § | NGS | 0/78 | 0/40 | 0/38 | - |
| Wang et al., 2020 [83] | Multicenter, retrospective | 406 ^ (279 MDS cases) | 50 (18–74) ** | 26/13 ** | NGS/PCR | 0/39 ** | 0/39 ** | - | - |
| Badar et al., 2020 [44] | Monocenter, retrospective | 646 ^ (310 MDS cases) | 72 (MDS cases) | NA | NGS | 4/263 (1.5%) | 4/263 (1.5%) | - | - |
| Yu et al., 2020 [84] | Monocenter, retrospective | 93 | 46 (16–87) | 56/37 | NGS | 1/93 (1.1%) | 1/93 (1.1%) | - | - |
| Wu et al., 2020 [85] | Monocenter, retrospective | 194 | 52 (28–66) ^^ | 7/5 ^^ | PCR/NGS | 12/194 (6.2%) | 12/194 (6.2% | - | - |
| Yun et al., 2020 [86] | Monocenter, prospective | 157 (95 MDS, CMML 10, sAML 52 cases)^ | 67 (40–90) § | 93/64 § | NGS | 8/157 (5%) ^ | - | - | - |
MDS, myelodysplastic syndrome; MDS/MPN, myelodysplastic/myeloproliferative neoplasm; MNs, myeloid neoplasms; CMML, chronic myelomonocytic leukemia; NA; not available; PCR, polymerase chain reaction; NGS, next generation sequencing; WGA, whole genome amplification; WGS, whole genome sequencing; sAML, secondary acute myeloid leukemia. * The entire patient cohort also included AML and MPN cases. ^ The entire patient cohort included also AML cases. ° Only therapy-related MNs were examined in this series. § Demographics refer to the entire patient cohort. ** Results refer to 39 RUNX1-mutated MDS cases only ^^ Information provided refers to NPM1-mutated cases only §§ Data refer to 125 patients who had at least one detectable pathogenic somatic mutations °° Results from previously published data sets are included in the final analysis *** The entire cohort also included patients with undefined cytopenia or aplastic anemia.