Table I.
Mutational spectrum, WBC, PLT and monocyte counts, CD34+ absolute count and apoptotic rate, CFU-GM from peripheral blood in a series of NS, NS/MPD and JMML patients.
| Patient | Mutated gene | Mutation | Hypersensitivity to GM-CSF | Unstimulated colony growth | Annexin V+/CD34+ (%) | CD34 (/μl) | WBC (103/μl) | Monocytes (103/μl) | PLT (103/μl) | ||
|---|---|---|---|---|---|---|---|---|---|---|---|
| NS1 | PTPN11 | Gln79Arg | No | No | 8.5 | L | 3.6 | N | 11.9 | 0.740 | 284 |
| NS2 | PTPN11 | Asn58His | No | No | 26.1 | H | 7 | N | 11.6 | 0.400 | 262 |
| NS3 | PTPN11 | Tyr63Cys | No | No | 16.1 | N | 2.5 | L | 8.3 | 0.300 | 428 |
| NS4 | PTPN11 | Gly503Arg | No | No | 2.56 | L | 3.42 | L | 17.1 | 1.720 | 331 |
| NS5 | PTPN11 | Gly503Glu | No | No | 7.6 | L | 3.6 | N | 7.3 | 0.900 | 249 |
| NS6 | PTPN11 | Asn308Ser | No | No | 12 | L | 6.2 | H | 10.3 | 0.690 | 297 |
| NS7 | PTPN11 | Leu261His | No | No | 10 | L | 2.9 | N | 5.8 | 0.470 | 416 |
| NS8 | PTPN11 | Leu261His | No | No | 0 | L | 4.8 | N | 12.0 | 0.770 | 376 |
| NS9 | PTPN11 | Leu261His | No | No | 10 | L | 17.52 | H | 7.3 | 0.600 | 277 |
| NS10 | PTPN11 | Phe285Ile | No | No | 7.9 | L | 3.8 | N | 7.7 | 0.410 | 218 |
| NS11 | PTPN11 | Glu76Asp | Yes | Yes | 1.0 | L | 12 | H | 12.0 | 1.140 | 300 |
| NS12 | PTPN11 | Glu139Asp | No | No | 17.8 | L | 2.2 | L | 7.3 | 0.510 | 198 |
| NS13 | PTPN11 | Asp61Asn | Yes | No | 4.1 | L | 13.8 | H | 15.3 | 0.840 | 212 |
| NS14 | SOS | Ile252Thr | No | No | 27.7 | H | 2.6 | L | 6.4 | 0.450 | 259 |
| NS15 | SOS | Thr266Lys | No | No | 8.8 | L | 16.2 | H | 12.5 | 0.620 | 291 |
| NS16 | SOS | Arg552Gly | No | No | 18.2 | L | 1.3 | L | 4.3 | 0.340 | 259 |
| NS17 | SOS | Glu433Lys | No | No | 0 | L | 7.75 | N | 15.5 | 1.420 | 422 |
| NS18 | RAF1 | Ser257Leu | No | No | 8 | L | 2.5 | L | 6.4 | 0.540 | 253 |
| NS19 | SOS | Met269Thr | Yes | No | 4.4 | L | 5.2 | N | 8.7 | 1.100 | 182 |
| NS20 | n.d. | n.d. | No | No | 11.2 | N | 4.5 | L | 12.2 | 1.110 | 184 |
| NS21 | KRAS | Gln22Arg | No | No | 15.7 | L | 5.6 | N | 9.44 | 0.630 | 551 |
| NS22 | BRAF | Leu597Val | No | No | 0.09 | L | 7.1 | H | 7.9 | 1.600 | 397 |
| NS23 | RAF1 | Pro261Ser | No | No | 25 | H | 5 | N | 12.6 | 1.450 | 384 |
| NS24 | SHOC2 | Ser2Gly | No | No | 6.8 | L | 8.5 | N | 17.0 | 0.700 | 482 |
| NS/MPD1 | PTPN11 | Phe285Ser | Yes | Yes | 2.4 | L | 58.0 | H | 14.5 | 2.500 | 399 |
| NS/MPD2 | PTPN11 | Asp61Asn | Yes | Yes | 0.2 | L | 1,374 | H | 43.5 | 5.520 | 54 |
| NS/MPD3 | PTPN11 | Asp61Asn | Yes | No | 1.6 | L | 205.7 | H | 20.2 | 2.550 | 167 |
| JMML1 | n.d. | n.d. | Yes | Yes | 2.1 | L | 193.6 | H | 9.3 | 1.900 | 55 |
| JMML2 | PTPN11 | Glu76Gly | Yes | Yes | 12.1 | N | 44 | H | 8.8 | 1.380 | 31 |
| JMML3 | PTPN11 | Gly503Val | Yes | No | 7.2 | L | 49.6 | H | 3.1 | 1.070 | 45 |
| JMML4 | NF1 | n.d. | Yes | Yes | 0.4 | L | 109.8 | H | 11.2 | 1.430 | 15 |
| JMML5 | n.m. | n.d. | Yes | Yes | 0.4 | L | 232 | H | 36.2 | 7.610 | 71 |
NS, Noonan syndrome patients (n=24); NS/MPD, Noonan syndrome patients with myeloproliferative evolution (n=3); JMML, juvenile myelomonocytic leukemia patients (n=5). For ‘% AnnexinV+/CD34+’ and ‘CD34+/μl’ categories: ‘L’ (low), indicated samples in which the values of Annexin V expression on CD34+ cells or the CD34+ absolute count were lower than the average −2 SD, compared to the reference values for the same age groups (reviewed in ref. 25); ‘N’ (normal) indicated samples in which the value was included in the average values ± 1 SD; ‘H’ (high) indicated samples in which the value was higher than the average +2 SD. Patient NS/MPD3 developed GM-CSF hypersensitivity during follow-up (Table IV). WBC, white blood count; PLT, platelets. n.d., not determined; n.m., no mutation.