Table 2.
Spectrum of molecular abnormalities in myelodysplastic syndromes with ring sideroblasts and single lineage dysplasia (RARS) and MDS/MPN with ring sideroblasts and thrombocytosis (RARS-T)
| Mutations and Study | RARS | RARS-T | Additional Myeloid neoplasms evaluated | Prognostic Impact |
|---|---|---|---|---|
|
| ||||
| JAK2V617F mutation: | ||||
| 1. Szpurka et al. Blood 2006[76] | 0/13 (0%) | 6/9 (67%) | RCMD-RS -0/16 (0%) RAEB-1/25 (4%) MDS with isolated del (5q) - 0/4 (0%) MDS-U-0/7 (0%) CMML-2/22 (9%) MDS/MPN-U – 3/26 (12%) Secondary AML-1/24 (4%) CML-0/21 (0%) PV-36/40 (90%) ET-17/30 (27%) PMF-18/33 (55%) |
|
| 2. Renneville et al. Leukemia 2006[77] | 0/7 (0%) | 5/7 (71%) | RAEB – 1/28 (4%) AML/MDS-1/9 (11%) CMML-2/15 (13%) ET-78/148 (53%) PV-86/92 (93%) PMF-30/50 (60%) |
|
| 3. Malcovati et al. Blood 2009[78] | 0/24 (0%) | 10/19 (53%) | ||
| 4. Broseus et al. Leukemia 2014[64] | 47/95 (49.4%) | |||
| 5. Jeromin et al. Haematologica 2014 [61] | 54/92 (58.7%) | |||
|
| ||||
| CALR Exon 9 mutation: | ||||
| 1. Klampf et al NEJM 2013[62] | 0% | 3/24 (12.5%) | MDS-0% AML-0% CMML-0% ET-25% PMF-35% PV-0% |
In PMF CALR mutations associated with better OS. |
| 2. Nangalia et al. NEJM 2013[63] | 3/27(11%) | 0/6 (0%) | Refractory anemia-9% RAEB-2/17-12% RA (5q−)-0% RCMD-0% RCMD-RS-0% ET-80/250 (32%) PMF-18/129 (14%) |
CALR mutations associated with higher platelet counts and lower hemoglobin |
| 3. Patnaik et al. Leukemia 2014[32] | 0/53 (0%) | |||
| 4. Broseus et al. Leukemia 2014[64] | 1/95 (1%) | |||
|
| ||||
| MPL mutations: | ||||
| 1. Malcovati et al. Blood 2009[78] | 1/19 (5%) | |||
| 2. Broseus et al. Leukemia 2014[64] | 1.1% (n=88) | |||
| 3. Jeromin et al. Haematologica 2014[61] | 2/92 (2.2%) | |||
|
| ||||
| SF3B1 mutations | ||||
| 1. Yoshida et al., Nature 2011 [17] | n=23 19/23 (82.6%) |
MDS without RS-6.5% RCMD-RS-38/50 (76% CMML -4.5% AML/MDS-4.8% De Novo AML-2.6% MPN-0% |
||
| 2. Papaemmanuil et al. NJEM 2011 [16] | 9/91 (10%) | RCMD-RS-13/23(56.5%) RCMD-3/53(6%) RAEB-6/110 (5%) PV-0% ET-6/189 (3%) PMF-6/136 (4.4%) CMML-5/106 (4.7%) |
Better OS- (p=0.01) Longer EFS (p=0.008) Longer LFS- (p=0.05) |
|
| 3. Patnaik et al. Blood 2012 [15] | 35 (66%) | RCMD (30%) RAEB-1 (4%) RAEB-2(0%) |
No benefit with regard to OS or LFS (p=0.6 and 0.2 respectively) | |
| 4. Visconte et al. Leukemia 2012 [79] | 9/14 (64%) | 13/18 (72%) | ||
| 5. Broseus et al. Leukemia 2014 [64] | 88.3% (n=94) | |||
| 6. Malcovati et al. Blood 2014[80] | 31/34 (91.2%) | NA | RCMD-RS - 16/28 (57.1%) RCMD-1 RA-3 |
SF3B1 mutations were associated with better survival (OS and LFS). |
| 7. Jeromin et al. Haematologica 2014[61] | 83/92 (90%) | |||
| 8. Patnaik et al Leukemia 2016 [23] | 41/48 (85%) | SF3B1 mutations were associated with inferior TFS. | ||
|
| ||||
| SRSF2 mutations: | ||||
| 1. Yoshida et al., Leukemia 2011[17] | 5.5% | NA | MDS with our RS-11.6% CMML-28.4% AML/MDS-6.5% De novo AML-2.6% MPN-1.9% |
|
| 2. Jeromin et al. Haematologica 2014[61] | 5/88 (5.7%) | |||
| 3. Patnaik et al. Leukemia 2016 [23] | 2/48 (4%) | |||
|
| ||||
| U2AF1 mutations: | ||||
| 1. Yoshida et al., Leukemia 2011[17] | 0% | NA | MDS without RS-11.6% CMML-8.0% AML/MDS-9.7% De novo AML-1.3% MPN-1.3% |
|
| 2. Jeromin et al. Haematologica 2014[61] | 4/89 (4.5%) | |||
|
| ||||
| TET2 mutations: | ||||
| 1. Jeromin et al. Haematologica 2014[61] | 21/90 (23.3%) | |||
| 2. Patnaik et al. Leukemia 2016 [23] | 5/48 (10%) | |||
|
| ||||
| DNMT3A mutations: | ||||
| 1. Jeromin et al. Haematologica 2014[61] | 13/78 (16.7%) | |||
| 2. Patnaik et al. Leukemia 2016 [23] | 6/48 (13%) | |||
|
| ||||
| ASXL1 mutations: | ||||
| 1. Jeromin et al. Haematologica 2014[61] | 13/91 (14.3%) | |||
| 2. Patnaik et al. Leukemia 2016 [23] | 14/42 (29%) | |||
Key: RARS, Refractory anemia with ringed sideroblasts; RARS-T, Refractory anemia with ringed sideroblasts and thrombocytosis, MDS, Myelodysplastic syndrome; RAEB, refractory anemia with excess blasts, CMML, Chronic myelomonocytic anemia; MPN, Myeloproliferative neoplasms; PV, polycythemia vera; PMF, primary myelofibrosis; ET, essential thrombocythemia; RCMD, refractory cytopenia with multilineage dysplasia; AML, acute myeloid leukemia; RA, refractory anemia; RS, ringed sideroblasts; OS, Overall survival; LFS, Leukemia free survival; TFS- Thrombosis free survival; WHO- World Health Organization.