Table 1. Clinical and laboratory data of patients treated with cytoreductive drugs and carrying TP53 mutations.
Disease type and course |
Therapy |
Mutations |
Follow-up |
|||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Therapy group | Sample | Driver mutation a | Sex | Disease phenotype | Age at sampling | Time from dg to study enrollment (mo) | Total therapy length (mo) | Therapy at sampling | HU therapy (mo) | IFN therapy (mo) | ANG therapy (mo) | Busulfan or chemo/radio therapy | Most abundant mutation (VAF %) | TP53 mutations (VAF %) | Follow-up from study enrollment (mo) | Outcome |
no HU | MP315 | JAK2 | M | PV | 62 | 109 | 89 | I | 0 | 0 | 0 | no | 0.8 | p.Y126D 0.79 | 39 | Alive |
048C | JAK2 | M | PV | 73 | 145 | 96 | I | 0 | 96 | 0 | no | 0.8 | p.E285K 0.82 | 41 | Alive | |
JAK1716 | JAK2 | F | PV | 63 | 111 | 110 | I | 0 | 110 | 0 | no | 0.2 | p.C238S 0.20 | 83 | Alive | |
MP189 | CALR+JAK2 | F | ET | 67 | 138 | 112 | A | 0 | 0 | 112 | no | 2.9 | p.P58A 2.90 | 51 | Alive | |
MP247 | CALR | F | PMF | 56 | 122 | 119 | A | 0 | 5 | 115 | no | 0.3 | p.Y220C 0.26 | 48 | Alive | |
MP155 | CALR | F | PMF | 61 | 122 | 121 | A | 0 | 0 | 121 | no | 0.2 | p.V143E 0.21 | 52 | Alive | |
227A | CALR | M | PMF | 72 | 154 | 123 | I | 0 | 123 | 0 | CH | 0.3 | p.A138V 0.26 | 10 | Dead | |
65A | CALR | F | ET | 70 | 158 | 152 | IA | 0 | 152 | 11 | no | 1.7 | c.376-2A>G 1.71; p.R273H 0.2 | 121 | Alive | |
186A | JAK2 | F | ET | 80 | 180 | 175 | I | 0 | 175 | 0 | no | 8.3 | c.454dupC 8.27 | 37 | Dead-AMLb | |
221A | CALR | M | ET | 69 | 180 | 179 | I | 0 | 179 | 0 | no | 2.2 | p.I162S 2.24 | 118 | Alive | |
HU <4y | MP15 | JAK2 | M | PV | 66 | 84 | 84 | I | 17 | 77 | 0 | no | 4.4 | p.Y220C 4.4 | 62 | Alive |
MP160 | JAK2 | M | ET | 69 | 61 | 18 | H | 18 | 0 | 0 | no | 0.2 | p.P142R 0.23 | 52 | Alive | |
MP68 | JAK2 | F | MPN | 70 | 58 | 56 | H | 47 | 0 | 9 | no | 6.9 | p.R248Q 6.90; p.A159V 6.40; p.P151R 1.73; p.I195S 0.24; p.R273H 0.23 | 44 | Dead-AMLc | |
HU ⩾4y | MP326 | JAK2 | F | PV | 58 | 80 | 48 | H | 48 | 0 | 0 | no | 0.6 | p.Y220C 0.55 | 39 | Alive |
MP345 | JAK2 | M | PV | 68 | 50 | 48 | H | 48 | 0 | 0 | no | 1.1 | p.S215R 1.10 | 38 | Alive | |
MP302 | JAK2 | F | PV | 71 | 231 | 65 | H | 56 | 0 | 0 | B | 0.4 | p.G199E 0.44 | 29 | Alive | |
MP319 | JAK2 | M | PV | 61 | 62 | 57 | HA | 57 | 0 | 32 | no | 0.4 | p.R273H 0.37 | 28 | Alive | |
MP168 | JAK2 | F | PV | 68 | 86 | 57 | H | 57 | 0 | 0 | no | 1.0 | p.H179R 0.95 | 49 | Alive | |
MP153 | JAK2 | M | PV | 63 | 62 | 61 | HA | 60 | 0 | 61 | no | 0.2 | p.R213G 0.23 | 51 | Alive | |
MP96 | JAK2 | F | PV | 55 | 64 | 62 | H | 62 | 0 | 0 | no | 0.5 | p.I195T 0.51; p.R282W 0.20 | 54 | Alive | |
MP327 | JAK2 | F | ET | 73 | 125 | 64 | H | 64 | 0 | 0 | no | 0.5 | p.R273H 0.47 | 39 | Alive | |
MP317 | CALR | M | PMF | 81 | 65 | 65 | H | 65 | 0 | 0 | no | 0.8 | p.V216M 0.83; p.H179R 0.25 | 17 | Dead | |
MP63 | JAK2 | F | ET | 68 | 79 | 69 | H | 69 | 0 | 0 | no | 0.2 | p.M246V 0.20 | 53 | Alive | |
MP5 | JAK2 | M | PV | 68 | 70 | 70 | H | 70 | 0 | 0 | no | 0.3 | p.I195T 0.26 | 64 | Alive | |
MP10 | JAK2 | M | PMF | 79 | 77 | 76 | H | 76 | 0 | 0 | no | 10.5 | p.G245S 10.50; p.R158H 0.54; p.H168R 0.29; p.F134L 0.23; p.Y234H 0.21 | 46 | Dead-expansiond | |
MP307 | MPL | F | PV | 82 | 103 | 76 | H | 76 | 0 | 0 | no | 0.2 | c.572_574del 0.21 | 40 | Alive | |
MP369 | JAK2 | F | PV | 73 | 84 | 81 | H | 81 | 0 | 0 | no | 1.4 | p.T170M 1.39 | 35 | Alive | |
MP246 | JAK2 | F | ET | 71 | 108 | 103 | A | 82 | 0 | 30 | no | 0.2 | p.D259H 0.2; p.G245S 0.2 | 48 | Alive | |
MP314 | JAK2 | F | PV | 69 | 233 | 92 | H | 86 | 0 | 0 | B | 1.3 | p.C242Y 1.26; p.G245D 0.35 | 39 | Alive | |
MP8 | JAK2 | M | PV | 82 | 92 | 90 | H | 90 | 0 | 0 | no | 0.2 | p.R175H 0.24 | 49 | Dead | |
MP356 | JAK2 | F | ET | 69 | 109 | 91 | H | 91 | 0 | 0 | no | 1.6 | p.R248Q 1.64 | 37 | Alive | |
MP230 | JAK2 | M | MPN | 70 | 96 | 96 | H | 96 | 0 | 0 | no | 0.5 | p.R248Q 0.50; c.512_514dup 0.22; p.V274G 0.20 | 22 | Dead | |
MP289 | JAK2 | F | PV | 61 | 265 | 140 | no | 98 | 42 | 0 | no | 3.3 | p.R213* 3.29; p.I251T 0.93; p.Y234H 0.67 | 39 | Alive | |
MP273 | JAK2 | F | ET | 75 | 111 | 111 | H | 111 | 0 | 0 | no | 0.3 | p.C176S 0.31; p.S240G 0.22 | 47 | Alive | |
MP229 | JAK2 | F | PMF | 85 | 112 | 112 | H | 112 | 0 | 0 | no | 1.0 | c.376-1G>A 0.95 | 49 | Alive | |
MP363 | JAK2 | M | ET | 87 | 117 | 112 | H | 112 | 0 | 0 | no | 0.3 | p.R248Q 0.29 | 37 | Alive | |
MP7 | JAK2 | F | PV | 69 | 133 | 130 | H | 121 | 9 | 0 | no | 0.5 | p.I255T 0.46 | 64 | Alive | |
MP329 | JAK2 | F | ET | 73 | 162 | 142 | H | 142 | 0 | 0 | no | 2.6 | p.R248W 2.61 | 27 | Alive | |
MP250 | JAK2 | F | PV | 74 | 152 | 152 | H | 152 | 0 | 0 | no | 0.4 | p.W91* 0.36 | 11 | Dead | |
MP2 | CALR | F | ET | 68 | 195 | 186 | HA | 169 | 11 | 110 | no | 11.6 | p.E286K 11.60; p.R248Q 0.45 | 67 | Alive | |
MP324 | JAK2 | M | PV | 72 | 255 | 255 | H | 255 | 0 | 0 | no | 0.3 | p.T253A 0.26 | 15 | Dead |
Abbreviations: A/ANG, anagrelide; B, busulphan; CH, chemotherapy; ET, essencial thrombocythemia; F, female; H/HU, hydroxyurea; I/IFN, interferon alpha; M, male; mo, months; PMF, primary myelofibrosis; PV, polycythemia vera; R, radiotherapy; y, years.
All three driver genes (JAK2 V617F+exon 12, CALR exon 9 and MPL exon 10) were sequenced in all patients with TP53 mutation.
Sample from leukemic transformation not available.
sAML JAK2-wt/TP53-wt.
Clonal expansion without leukemic transformation.