Table 1.

TKI resistance mutations identified by Duplex Sequencing

Patient numberGenomes sequencedResistance mutations identified by Duplex Sequencinga
Initial diagnosis14,001
226,076
3973
44,403
520,805
64,486
727,072M472I (0.004%)
84,021
94,921
103,436
111,746
122,318
136,249
149,294
159,033
166,319
Highly refractory CP-CML254,074G250E (0.021%)
265,905E355Ab (39.61%), L248V (0.032%), T315I (0.10%), A397P (0.083%), F486S (0.017%)
276,722T315Ib (4.36%), K247R (0.014%), L248V (0.014%), V299L (0.016%)
288,065T315Ib (4.30%) F317Lb (28.25%) F359Cb (31.62%)
294,868
305,035M244Vb (1.70%), F359Vb (31.68%), Y253H (0.019%), G250E (0.19%)
314,753
324,369
334,844V299Lb (42.45%), F359Vb (42.94%), Y253H (0.014%)
Highly refractory AP-CML346,201F317Lc (37.74%), G250E (0.051%), F317Ld (1.78%)
354,348
364,370G250Ec (2.37%), M351Tc (27.10%), E275K (0.30%), F317L (0.085%)
Highly refractory BP-CML373,297
387,292Y253Hc (53.72%)
393,574E255Kc (45.66%), Q252H (0.020%), E255V (1.02%), E459K (0.28%)
403,681G250Ec (17.46%), V299Lc (25.88%)
414,833F317Lc (25.90%), F359Vc (30.43%), F359I (1.58%)
425,179L248V (0.015%), T315I (0.020%)
433,946F359Cc (40.72%), M237V (0.020%), E255V (0.042%)
446,509F359Cc (27.16%)
455,447T315Ic (20.19%), L387F (0.017%)
465,206T315Ic (30.11%)
479,879G250Ec (45.89%), T315A (45.91%) H396R (0.010%)
Highly refractory Ph+ ALL481,648T315Ic (2.28%)
495,125F317I (48.54%), V299L (0.026%), V299Ld (1.26%)
501,171T315Ic (37.63%)
513,186F317Ic (4.67%)
523,595T315Ic (3.35%)
535,136G250Ec (27.09%), F317Lc (57.74%), T315I (0.21%), F359V (2.02%), H396P (0.034%)
545,094T315Ic (0.28%), F317Lc (0.073%)
  • a"Highly refractory" patients additionally had mutation detection performed by NGS or Sanger sequencing. Resistance mutations identified by Duplex Sequencing which were not revealed by NGS/Sanger are bolded and underlined.

  • bMutation was also identified by conventional NGS.

  • cMutation was also identified by Sanger sequencing.

  • dSame amino acid mutation encoded by a distinct nucleotide substitution.