sampleID ptInitials collDate mutation Patient.initials Gender Age.at.Nil.Das.start..yrs. Imatinib.resistant..intolerant Disease.Phase X2TKI.therapy Date.of.First.Nilotinib.Dasatinib.Imatinib Follow.up..months. Response.at.end.of.study.or.last.sample.received Achieved.a.CCyR. Mo.of.CCyR. Mutation.at.start.of.Nilotinib.Dasatinib.by.Direct.Sequencing X..Mutations.by.Direct.Sequencing.at.start.of.Nil.Das Mutations.detected.by.MassArray.at.start.of.Nilotinib.Dasatinib.in.replicate.samples X..Mutations.detected.by.MassArray.at.start.of.Nil.Das new.mutations.that.emerged.during.nilotinib.or.dasatinib.therapy..OR.Imatinib.for.IC...MT. Month.of.1st.new.mutation Group.4.Sample.Notes.if.Applicable 1 JJB 15/9/05 e255v.gtg,e355g.ggg:2|e255v.gtg,t315i.att:2 JJB M 29 resistant CP nilotinib 38610 15 failure - no cyto resp 3m NA M244V 5%, E255V 60% T315I 15% 3 E255V E355G M244V G250E Q252H(G>C) T315I E255K 7 NA 2 LAJ 1/6/05 m351t.acg,f486s.tct:1 LAJ F 62.6082191780822 resistant CP dasatinib 38504 10 progression NA M351T 90%, H396R 5% 2 E255V M351T H396R F486S F359V G250E L248V E459K 8 F317L (949T>C, 951 C>G, 951C>A) 6 3 CAN 27/6/05 CAN F 21.5643835616438 resistant CP dasatinib 38530 12 lost CCyR - toxicity Y 6 M244V 75%, L248V 35% 2 M351T Y253H E355G M244V G250E L248V 6 NA 4 GC 5/7/05 w235r.cgg,g250e.gag:1 GC M 61.7013698630137 resistant CP dasatinib 38538 29 lost CCyR Y 3 G250E 100%, M244V 5% 2 M244V G250E 2 NA 5 KM 5/7/05 g250e.gag,e255k.aag:1 KM M 54.4109589041096 resistant CP dasatinib 38538 24 CCyR Y 3 G250E 20%, E255K 100% 2 G250E E255K 2 NA 6 EAD 5/1/06 g250e.gag,e255k.aag:2 EAD 30 resistant AP nilotinib 38722 6 no MCyR NA G250E 15%, E255K 70% 2 E255V H396R G250E E459K E255K 5 E255V 6 7 CHL 26/4/06 q252h.cac,f359v.gtc:1 CHL 52 resistant AP nilotinib 38833 12 no MCyR NA Q252H (G>C) 70%, D276G 20%, 829 T>A 20%, F359V 5% 4 F359V Q252H(G>C) *D276G not detected due to T277S on same clone 2 F359V 1 8 NA NA NA CL 73 resistant AP nilotinib 38874 6 no MCyR NA E255K 85%, 1189G>C 15% 2 E255K 1 NA 9 VV 7/3/05 m244v.gtg,h396r.cgt:3|h396r.cgt,e450g.ggg:1 VV F 74.7561643835616 resistant AP dasatinib 38418 21 CCyR Y 21 H396R 70%, M244V 10% 2 H396R M244V 2 NA 10 KSB 30/3/05 KSB M 58.3260273972603 resistant AP dasatinib 38441 35 MCyR Y 3 E355G 75%, F359V 25% 2 F359V E355G M244V 3 T315I, M244V 3 11 YRC 21/4/05 g249d.gac,e255v.gtg:3|m244v.gtg,e355a.gcg:2|m244v.gtg,e459k.aag:1 YRC M 52.5369863013699 resistant AP dasatinib 38463 24 no MCyR NA M244V 50%, E255V 10%, M351T 10% 3 E255V M351T F486S M244V E279K L248V E459K 1064A>C (E355A) 8 L248V/ E355A/T315I 24 12 LAB 21/4/05 y253h.cac,a397p.cct:2 LAB M 63.5424657534247 resistant AP dasatinib 38463 30 MMR Y 3 Y253H 50%, A397P 60% 2 M351T F317L(949T>C) Y253H 3 F317L 22 13 SAK 16/5/05 t315i.att,f359v.gtc:2 SAK M 35.4958904109589 resistant AP dasatinib 38488 3 no MCyR NA T315I 25%, F359V 70% 2 F359V T315I 2 NA 14 GLL 30/5/05 GLL F 47.4328767123288 resistant AP dasatinib 38502 18 no MCyR NA H396R 30%, A397P 15% 2 H396R F359I F359V Y253F 4 T315I 15 15 MAP 6/6/05 t315i.att,s417y.tac:1|g250e.gag,t315i.att:1 MAP M 59.6219178082192 resistant AP dasatinib 38509 1 no MCyR NA T315I 60%, G250E 10%, M351T 5%, H396R 5%, S417Y <5% 4 M351T H396R F359V Y253F M244V F359C G250E L248V T315I 9 NA 16 JHC 16/6/05 h396r.cgt,e453k.aag:1 JHC M 47.4465753424658 resistant AP dasatinib 38519 33 no MCyR NA H396R 15%, E453K 50% 2 M351T H396R M244V 3 NA 17 SP 23/6/05 SP M 22.1835616438356 resistant AP dasatinib 38526 7 no MCyR NA T315I 45% 3 M351T H396R F317L(951C>A) L248V T315I E459K 6 NA 18 DAJ 29/8/05 y253f.ttc,f359i.atc:8 DAJ 51 resistant BC nilotinib 38593 3 no MCyR NA Y253F 65%, F359I 35% 2 F359I Y253F 2 NA 19 LCM 5/4/06 LCM 36 resistant BC nilotinib 38812 1 no MCyR NA G250E 15%, T315I 40% 2 F317L(951C>A) G250E T315I 3 NA 20 PMP 28/3/05 f359v.gtc,m472i.ata:2 PMP NA resistant BC dasatinib 38439 8 no MCyR NA 1416G>A 90%, F359V <5% 2 H396R F359V 2 F317L 100% 6 21 CSC 26/4/05 t315i.att,h396r.cgt:3|h396r.cgt,p465s.tca:1 CSC NA resistant BC dasatinib 38468 2 no MCyR NA H396R 90%, T315I 25% 2 H396R T315I 2 NA 22 VAP 18/5/05 VAP NA resistant Ph+ ALL/LBC dasatinib 38490 4 no MCyR NA M244V 30%, G250E 35%, Y253F 35% 3 E255V Y253F M244V F359C F317L(951C>A) G250E L248V E459K 8 V299L, F317L(951C>A) 4 23 NA NA NA LCG NA resistant Ph+ ALL/LBC dasatinib 38516 4 no MCyR NA Y253H 55%, M351T <10% 2 M351T H396R F486S F359V Y253H M244V G250E L248V E459K 9 F317L 4 24 IC 7/26/2010 IC F 57.3 newly diagnosed CP none- imatinib first line 40385 12 failure- mut at 3 months Y 3 NA NA Q252H 30%, E255K 10%, E255V 3 25 MT 5/26/2009 e255k.aag,t315i.att:1|q252h.cac,t315i.att:1 MT M 37 newly diagnosed CP none- imatinib first line 39959 4 Progression to BC at 4 mo N NA NA NA Q252H 30%,Y253H 15%,E255K 20%,T315I 30% 3 26 PMR 27/7/05 PMR 55 resistant CP nilotinib 38560 21 progression NA M244V 60% 1 M244V 1 G250E/T315I 18 27 LE 12/10/05 LE M 65 resistant CP nilotinib 38637 8 progression NA F359V 100% 1 F359V 1 NA 28 DLP 19/10/05 e279k.aag,l387m.atg:3 DLP F 69 resistant CP nilotinib 38644 21 CCyR Y 6 E279K 100% 1 E279K 1 NA 29 CRE 1/5/06 t315i.att,a412s.tcc:1 CRE 65 resistant CP nilotinib 38838 3 progression NA T315I 100% 1 T315I F317L (951 C>A) 2 NA 30 NA NA NA DFF 69 resistant CP nilotinib 38784 18 failure - no cyto resp 6m NA M351T 90% 1 M351T F486S F317L (951C>A) 3 F317L 4 31 GR 7/4/06 m351t.acg,h396r.cgt:2 GR 45 resistant CP nilotinib 38814 3 failure - no cyto resp 3m NA M351T 70% 1 M351T H396R F359I E355G G250E 5 G250E, F359I BM only/H396R 3 32 REL 1/9/05 REL 60 resistant CP nilotinib 38596 6 progression NA Y253H 100% 1 Y253H 1 NA 33 NA NA NA MF F 69.6493150684932 resistant CP dasatinib 38439 2 Minimal cyto response at 3m NA M351T 80% 1 M351T 1 NA 34 KA 9/4/05 KA F 45.9068493150685 resistant CP dasatinib 38451 32 CCyR Y 3 G250E 100% 1 G250E 1 NA 35 VL 5/5/05 VL M 64.8876712328767 resistant CP dasatinib 38477 24 failure - no cyto resp 3m NA E255V 100% 1 E255V 1 T315I 15 36 DHD 16/5/05 DHD F 65.2657534246575 resistant CP dasatinib 38488 17 achieved MCyR NA E459K 100% 1 E355G E459K G250E 3 F317L ?G250E 6 37 SF 31/5/05 SF F 44.586301369863 resistant CP dasatinib 38503 33 CCyR Y 3 A397P 100% 1 none 0 NA 38 IW 7/6/05 IW F 42.1178082191781 resistant CP dasatinib 38510 33 CCyR Y 3 E279K 25% 1 E279K 1 NA 39 BHK 24/5/05 t315i.att,l387f.ttc:4|e236*.tag,t315i.att:4|f283s.tcc,t315i.att:3|t315i.att,g372w.tgg,v377l.ttg:3|t315i.att,g372w.tgg:2|t315i.att,q346*.tag:2|f283s.tcc,t315i.att,d363y.tat:2|t315i.att,r386s.agt:2|t315i.att,d363y.tat:2 BHK M 31.641095890411 resistant AP dasatinib 38496 6 no MCyR NA T315I 90% 1 T315I 1 NA 40 JGK 24/5/05 JGK M 45.4493150684931 resistant AP dasatinib 38496 32 MMR Y 2 M351T 90% 1 M351T 1 NA 41 CWS 15/6/05 CWS M 24.2301369863014 resistant AP dasatinib 38518 33 lost MCyR Y 3 M351V (1051A>G) 90% 1 none 0 NA 42 RWB 7/11/05 RWB 64 resistant BC nilotinib 38663 2 no MCyR NA M244V 100% 1 M244V Q252H(G>C) 2 F359V Y253H E255K 1 43 RW 15/12/06 RW 29 resistant BC nilotinib 39066 3 no MCyR NA V299L (G>T) 70% 1 V299L(G>T) 1 NA 44 LY 20/6/06 LY 57 resistant BC nilotinib 38888 2 no MCyR NA L248V 100%, del ~20% 1 L248V 1 NA 45 DMJ 12/7/06 f317i.atc,w476c.tgt:2 DMJ 53 resistant BC nilotinib 38910 2 no MCyR NA F317I 100% 1 F317I V299L(G>T) 2 E255V 2 46 DKK 23/3/05 t315i.att,g463g.ggt:3|q252h.cac,t315i.att:3|t315i.att,e355g.ggg:2|r307w.tgg,t315i.att:2|e238e.gag,t315i.att:1 DKK NA resistant BC dasatinib 38434 1 no MCyR NA T315I 80% 1 Q252H(G>C) T315I 2 NA 47 MA 9/11/05 MA 70 resistant Ph+ ALL/LBC nilotinib 38665 3 no MCyR NA F317L (949T>C) 15% 1 F317L(949T>C) Y253H 2 Y253H 3 48 EAM 29/4/05 EAM NA resistant Ph+ ALL/LBC dasatinib 38471 27 CCyR Y 4 L248V 100%, del ~25% 1 L248V 1 NA 49 LAZ 6/3/06 LAZ F 45 resistant CP nilotinib 38782 3 progression NA D276G 50% 1 D276G T315I 2 T315I 1 50 SOP 31/10/06 g250e.gag,m351t.acg:2 SOP 69 resistant CP nilotinib 39021 10 progression NA G250E 30%, M351T 25% 2 E255V M351T G250E T315I F359V 5 E255V, T315I/F359V 1 51 DJS 1/4/05 DJS F 32.6520547945205 resistant CP dasatinib 38443 9 progression Y 3 G250E 75% 1 G250E 1 T315I 4 52 CPH 24/5/05 m244v.gtg,e355g.ggg:2|m244v.gtg,f359v.gtc:2|m244v.gtg,e459g.ggg:2 CPH M 56.0849315068493 resistant CP dasatinib 38496 11 MCyR Y 12 M244V 50%, Y253H 10% 1 F359V Y253H E355G M244V T315I E255K 6 Y253H, T315I, E255K 2 53 MHB 7/6/05 MHB M 43 resistant CP dasatinib 38510 10 Minimal cyto response NA no mutation 0 T315I 1 T315I 6 54 VMM 6/7/05 e355g.ggg,e453k.aag:1|t315i.att,e355g.ggg:1 VMM F 65.7150684931507 resistant CP dasatinib 38539 17 failure - no responseno cyto response 3m NA E355G 80% 1 F359V E355G T315I 3 T315I, F317L 2 55 MJK 20/7/05 MJK 33.4383561643836 resistant CP dasatinib 38553 4 progression NA no mutation 0 T315I 1 T315I 2 56 AD 31/3/05 AD F 63.5095890410959 resistant AP dasatinib 38442 18 no MCyR NA A397P 100% 1 T315I 1 T315I 3 57 AFN 2/5/05 e255k.aag,f359v.gtc:5|f359v.gtc,f486s.tct:3|e255k.aag,f486s.tct:2 AFN M 62.5808219178082 resistant AP dasatinib 38474 9 no MCyR NA E255K 25%, F359V 35% 2 E255V M351T F486S F359V M244V T315I E255K 7 M244V 9 58 JYN 20/6/05 JYN F 65.2465753424657 resistant AP dasatinib 38523 9 no MCyR NA S417Y 70% 1 E355G F317L(951C>G) T315I 3 T315I 9 59 ARS 2/11/05 ARS 66 intolerant BC nilotinib 38658 1 no MCyR NA no mutation 0 T315I 1 T315I 1 60 ABS 12/5/05 l248v.gtg,f486s.tct:2 ABS NA resistant BC dasatinib 38484 12 no MCyR NA L248V 60%, F486S <10% 2 M351T H396R F486S F359V E355G F359C G250E L248V T315I E459K 10 T315I 12 61 JHL 11/5/05 JHL NA resistant BC dasatinib 38483 1 no MCyR NA no mutation 0 T315I 1 T315I 1 62 AHP 10/10/06 c305r.cgc,f317l.ttg:2 AHP 75 resistant CP nilotinib 39000 6 failure - no cyto resp 3m NA F317L (951C>G) 100% 1 V299L(G>C) F317L(951C>G) 2 Q252H 4 63 AHP 5/12/06 g249s.agc,f317l.ttg:1|f317l.ttg,a412s.tcc:1 AHP 75 resistant CP nilotinib 39000 6 failure - no cyto resp 3m NA F317L (951C>G) 100% 1 V299L(G>C) F317L(951C>G) 2 Q252H 4 64 AHP 6/3/07 q252h.cac,f317l.ttg:2|f317l.ttg,d363y.tat:1|f317l.ttg,e450d.gat:1|v260v.gta,f317l.ttg:1 AHP 75 resistant CP nilotinib 39000 6 failure - no cyto resp 3m NA F317L (951C>G) 100% 1 V299L(G>C) F317L(951C>G) 2 Q252H 4 65 MZ 24/5/06 MZ 44 resistant CP nilotinib 38861 6 failure - no cyto resp 6m NA E355G 1 E355G 1 T315I 6 66 MZ 26/7/06 MZ 44 resistant CP nilotinib 38861 6 failure - no cyto resp 6m NA E355G 1 E355G 1 T315I 6 67 MZ 11/10/06 MZ 44 resistant CP nilotinib 38861 6 failure - no cyto resp 6m NA E355G 1 E355G 1 T315I 6 68 HL 1/6/05 q252h.cat,h396r.cgt:2|q252h.cat,r362i.ata:1|i242t.acc,q252h.cat:1|q252h.cat,g463s.agc:1 HL M 82.2164383561644 resistant CP dasatinib 38504 5 failure- mut at 3 months NA Q252H (G>T) 80%, E255K 15%, H396R 30% 3 H396R Q252H(G>T) E255K 3 T315I 4 69 HL 1/7/05 e255k.aag,h396r.cgt:1 HL M 82.2164383561644 resistant CP dasatinib 38504 5 failure- mut at 3 months NA Q252H (G>T) 80%, E255K 15%, H396R 30% 3 H396R Q252H(G>T) E255K 3 T315I 4 70 HL 1/8/05 e255k.aag,t315i.att:1|i242t.acc,e255k.aag:1 HL M 82.2164383561644 resistant CP dasatinib 38504 5 failure- mut at 3 months NA Q252H (G>T) 80%, E255K 15%, H396R 30% 3 H396R Q252H(G>T) E255K 3 T315I 4 71 HL 21/10/05 e255k.aag,t315i.att:8 HL M 82.2164383561644 resistant CP dasatinib 38504 5 failure- mut at 3 months NA Q252H (G>T) 80%, E255K 15%, H396R 30% 3 H396R Q252H(G>T) E255K 3 T315I 4 72 MDL 15/6/05 l248v.gtg,f359i.atc:1 MDL M 46.3205479452055 resistant CP dasatinib 38518 20 progression NA L248V 100% 1 F359I M244V L248V 3 V299L 6 73 MDL 02/12/05 l248v.gtg,v299l.ttg:1 MDL M 46.3205479452055 resistant CP dasatinib 38518 20 progression NA L248V 100% 1 F359I M244V L248V 3 V299L 6 74 MDL 28/2/07 l248v.gtg,v299l.ttg:3|v299l.ttg,s438p.ccc:1 MDL M 46.3205479452055 resistant CP dasatinib 38518 20 progression NA L248V 100% 1 F359I M244V L248V 3 V299L 6 75 CO 5/7/05 CO F 54.2712328767123 resistant CP dasatinib 38538 30 failure - no responseno cyto response 9m NA G250E 100% 1 G250E 1 F317L 24 76 CO 5/12/07 g250e.gag,f317l.ttg:51|g250e.gag,f317l.ttg,p439l.ctt:1 CO F 54.2712328767123 resistant CP dasatinib 38538 30 failure - no responseno cyto response 9m NA G250E 100% 1 G250E 1 F317L 24 77 LK 24/3/06 e236d.gat,e255k.aag:4 LK 75 resistant AP nilotinib 38800 9 no MCyR NA E255K 100% 1 Y253H E255K 2 Y253H 1 78 NA NA NA LK 75 resistant AP nilotinib 38800 9 no MCyR NA E255K 100% 1 Y253H E255K 2 Y253H 1 80 CSY 21/3/05 p230p.cca,f359c.tgc:1 CSY M 64.0739726027397 resistant AP dasatinib 38432 34 no MCyR NA F359C 100% 1 F359C 1 T315I 15 81 CSY 28/3/06 t315i.att,f359c.tgc:3|f359c.tgc,r460r.cgt:1 CSY M 64.0739726027397 resistant AP dasatinib 38432 34 no MCyR NA F359C 100% 1 F359C 1 T315I 15 82 CSY 22/1/08 t315i.att,f359c.tgc:45|t315i.att,a350a.gct,e352d.gat,f359c.tgc:6|t315i.att,a350a.gct,f359c.tgc:4|t315i.att,e352d.gat,f359c.tgc:2|t315i.att,a350a.gct,e352d.gat:1|t315i.att,a350a.gct:1 CSY M 64.0739726027397 resistant AP dasatinib 38432 34 no MCyR NA F359C 100% 1 F359C 1 T315I 15 83 JLR 29/4/05 y253h.cac,f317l.tta:2|f317l.tta,g321g.gga:1 JLR M 45.6876712328767 resistant AP dasatinib 38471 18 no MCyR NA Y253H 10%, F317L (951C>A) 90% 2 Y253H F317L(951C>A) 2 T315I 18 84 JLR 12/11/07 y253h.cac,f317l.ttg:14|y253h.cac,t315i.att:4|d276e.gag,t315i.att:1 JLR M 45.6876712328767 resistant AP dasatinib 38471 18 no MCyR NA Y253H 10%, F317L (951C>A) 90% 2 Y253H F317L(951C>A) 2 T315I 18 85 RE 4/5/05 RE F 61.3643835616438 resistant AP dasatinib 38476 16 no MCyR NA G250E 100% 1 H396R G250E 2 T315A 16 86 NA NA NA RE F 61.3643835616438 resistant AP dasatinib 38476 16 no MCyR NA G250E 100% 1 H396R G250E 2 T315A 16 87 NEF 16/5/05 p230p.cca,f359c.tgc:1 NEF F 48.9013698630137 resistant AP dasatinib 38488 16 no MCyR NA F359C 100% 1 F359C 1 V299L 16 88 NEF 25/9/06 v299l.ctg,f359c.tgc:12|v299l.ctg,f317l.ttg:1|v299l.ctg,f317l.ctc:1 NEF F 48.9013698630137 resistant AP dasatinib 38488 16 no MCyR NA F359C 100% 1 F359C 1 V299L 16 89 LYS 27/5/05 t240a.gcg,y253f.ttc:18|t240a.gcg,y253f.ttc,h396r.cgt:1 LYS M 63.7342465753425 resistant AP dasatinib 38499 5 no MCyR NA Y253F 90%, H396R 20%, T240A 80% 3 M351T H396R Y253F G250E 4 T240A 40%, G250E 60%, 5 90 NA NA NA LYS M 63.7342465753425 resistant AP dasatinib 38499 5 no MCyR NA Y253F 90%, H396R 20%, T240A 80% 3 M351T H396R Y253F G250E 4 T240A 40%, G250E 60%, 5 91 DVD 29/6/05 DVD F 60.3178082191781 resistant AP dasatinib 38532 18 no MCyR NA E279K 90% 1 E279K 1 T315I F317L 12 17 Nov 2006 Sample - Lost of MCyR 92 DVD 17/11/06 e279k.aag,t315i.att:5|e279k.aag,f317l.ttg:3|t315i.att,m458i.att:1 DVD F 60.3178082191781 resistant AP dasatinib 38532 18 no MCyR NA E279K 90% 1 E279K 1 T315I F317L 12 17 Nov 2006 Sample - Lost of MCyR 93 DVD 11/1/07 e279k.aag,t315i.att:6|e279k.aag,f317l.ttg:3|t315i.att,w478l.ttg:2|t315i.att,d482d.gat:1 DVD F 60.3178082191781 resistant AP dasatinib 38532 18 no MCyR NA E279K 90% 1 E279K 1 T315I F317L 12 17 Nov 2006 Sample - Lost of MCyR 94 BRM 21/12/05 m244v.gtg,d276g.ggc:1 BRM 46 resistant BC nilotinib 38707 5 no MCyR NA M244V 70% 1 D276G M244V 2 D276G/E255V 3 95 BRM 8/5/06 m244v.gtg,e255v.gtg:56 BRM 46 resistant BC nilotinib 38707 5 no MCyR NA M244V 70% 1 D276G M244V 2 D276G/E255V 3 96 EEC 25/4/05 g250e.gag,h396r.cgt:3|e279k.aag,h396r.cgt:2|h396r.cgt,f486s.tct:2 EEC NA resistant BC dasatinib 38467 8 no MCyR NA H396R 65%, G250E 15%, F486S 10% 3 H396R F486S G250E E279K 4 F317L x2 8 97 EEC 27/12/05 g250e.gag,f317l.tta:5|g250e.gag,f317l.ctc:3 EEC NA resistant BC dasatinib 38467 8 no MCyR NA H396R 65%, G250E 15%, F486S 10% 3 H396R F486S G250E E279K 4 F317L x2 8 98 DWB 14/6/05 DWB NA resistant BC dasatinib 38517 3 no MCyR NA M351T 100% 1 M351T 1 T315I 3 99 DWB 21/9/05 t315i.att,m351t.acg:22 DWB NA resistant BC dasatinib 38517 3 no MCyR NA M351T 100% 1 M351T 1 T315I 3 100 MT 2/17/2009 MT M 37 newly diagnosed CP none- imatinib first line 39959 4 Progression to BC at 4 mo N NA NA NA Q252H 30%,Y253H 15%,E255K 20%,T315I 30% 3