Comparison between mutations detected by SS and mutations detected by UDS and estimated clonal composition of the samples harboring multiple mutations as assessed by UDS
| Code . | Date . | TKI . | Line . | Mutations by SS . | Mutations by UDS* . | Estimated mutated populations by UDS† . | Disease status and response . |
|---|---|---|---|---|---|---|---|
| CP-01-01 | 2/29/2012 | DAS | 2 | H396R (∼50), F317L (∼30) | H396R (55.05), F317L (28.23) | H396R (43.99), F317L (17.17), H396R+F317L (11.06) | Complete cytogenetic response but no molecular response after 6 mo on DAS |
| CP-01-02 | 5/2/2012 | DAS | 2 | F317L (∼70), H396R (∼20) | F317L (63.07), H396R (15.74), T315I (5.42) | F317L (55.47),H396R (7.60), H396R+F317L (7.38), T315I (4.44), H396R+T315I (0.76), F317L+T315I (0.22) | Complete hematologic response, cytogenetic response not assessed |
| CP-01-03 | 7/7/2012 | NIL | 3 | T315I (∼100) | T315I (99.28) | T315I (99.28) | Complete hematologic response, no cytogenetic response |
| CP-02-01 | 3/4/2008 | IM | 1 | F359V (∼20) | F359V (17.33) | F359V (17.33) | Loss of complete hematologic response after 5 mo on IM |
| CP-02-02 | 4/2/2008 | DAS | 2 | T315I (∼100) | T315I (94.80) | T315I (94.80) | Progression to LBC |
| CP-03-01 | 3/7/2005 | IM | 1 | G250E (∼100) | G250E (93.72), F317L (1.78) | G250E (92.20), G250E+F317L (1.52), F317L (0.26) | Minor cytogenetic response after 12 mo on IM |
| CP-03-02 | 9/14/2005 | DAS | 2 | G250E (∼70), F317L (∼20) | G250E (74.71), F317L (22.51) | G250E (62.00), G250E+F317L (12.71), F317L (9.80) | Minor cytogenetic response |
| CP-03-03 | 11/17/2005 | DAS | 2 | G250E (∼70), F317L (∼30) | G250E (60.73), F317L (27.06) | G250E (46.44), G250E+F317L (14.29), F317L (12.77) | Not available |
| CP-03-04 | 2/13/2006 | DAS | 2 | G250E (∼50), F317L (∼40) | G250E (45.47), F317L (37.49), H295H (4.91), C330C (1.48) | G250E (30.46), F317L (20.40), G250E+F317L (12.47), F317L+H295H (2.14), G250E+F317L+H295H (1.19), H295H (0.89), F317L+C330C (0.82), G250E+H295H (0.69), G250E+F317L+C330C (0.47), G250E+C330C (0.19) | Complete hematologic response, no cytogenetic response |
| CP-03-05 | 5/15/2006 | NIL | 3 | G250E (∼100), E255E (∼100) | G250E (87.17), E255E (85.78), F317L (10.44) | G250E+E255E (77.90), G250E+F317L+E255E (7.66), F317L (2.56), G250E (1.61), F317L+E255E (0.22) | Complete hematologic response, no cytogenetic response |
| CP-04-01 | 10/20/2005 | IM | 1 | L384M (∼100) | L384M (87.04), E255V (15.14) | N.A. | Loss of complete cytogenetic response after 24 mo on IM |
| CP-04-02 | 12/22/2005 | NIL | 2 | L384M (∼70), E255V (∼30) | L384M (68.33), E255V (32.02), M351I (2.64) | N.A. | Loss of complete hematologic response |
| CP-04-03 | 1/24/2006 | NIL | 2 | E255V (∼100) | E255V (80.71), L384M (14.40) | N.A. | No hematologic response |
| CP-05-01 | 1/20/2005 | IM | 1 | G250E (∼100) | G250E (99.51) | G250E (99.51) | Loss of complete cytogenetic response after 36 mo on IM |
| CP-05-02 | 3/23/2005 | DAS | 2 | F317L (∼30), G250E (∼30) | F317L (24.93), G250E (22.89), C305C (11.70), K274E (10.38) | G250E (16.52), F317L (15.06), C305C (9.30), G250E+F317L (4.30), K274E (4.09) F317L+K274E (3.70), G250E+K274E (1.04), C305C+F317L (0.97), C305+CK274E (0.91), G250E+F317L+K274E (0.51), G250E+C305C+F317L (0.39), G250E+C305C+K274E (0.13) | Not available |
| CP-05-03 | 4/20/2005 | DAS | 2 | F317L (∼100) | F317L (99.50) | F317L (99.50) | Complete hematologic response, no cytogenetic response |
| CP-06-01 | 4/19/2005 | IM | 1 | H396R (∼100) | H396R (99.63), A413A (1.71), K247N (1.11) | N.A. | Partial cytogenetic response after 18 mo on IM |
| CP-06-02 | 5/17/2005 | DAS | 2 | None | H396R (16.07), F317L (7.43) | H396R (16.07), F317L (7.43) | Complete cytogenetic response (= 0/200 Ph+ by FISH) |
| CP-06-03 | 6/14/2005 | DAS | 2 | F317L (∼20) | F317L (20.86), H396R (3.54) | F317L (20.20), H396R (2.88), F317L+H396R (0.66) | Loss of complete cytogenetic response (= 30/200 Ph+ by FISH) |
| CP-07-01 | 3/22/2007 | IM | 1 | None | A433A (1.48), P408P (1.42), K378R (1.32) | A433A (1.48), P408P (1.42), K378R (1.32) | No cytogenetic response after 12 mo on IM |
| CP-07-02 | 9/8/2009 | NIL | 2 | T315I (∼30) | T315I (25.99), M351T (5.93), T345T (6.37), R332R (5.91) | T315I (20.47), T345T (6.15), R332R (5.75), T315I+M351T (5.30), M351T (0.47), T315I+T345T (0.22), M351T+R332R (0.16) | No cytogenetic response |
| CP-07-03 | 3/4/2010 | NIL | 2 | T315I (∼70) | T315I (65.85), Y253H (16.65), W235R (3.77), F497L (3.14), T406I (2.43), Q477Q (2.37), F486S (2.28), D363N (1.47) | N.A. | No cytogenetic response; transplanted 6 mo later |
| CP-08-01 | 6/22/2010 | IM | 1 | M351T (∼100), E499E (∼100) | M351T (99.84), E499E (99.84) | N.A. | No cytogenetic response after 12 mo on IM |
| CP-08-02 | 4/26/2012 | NIL | 2 | Y253H (∼100), E499E (∼100) | Y253H (95.64), E499E (99.67), M351T (3.20) | N.A. | No cytogenetic response |
| CP-09-01 | 6/22/2004 | IM | 1 | M244V (∼20) | M244V (19.4), H396R (2.88), L298V (1.91), L364I (1.64) | N.A. | No cytogenetic response after 15 mo on IM |
| CP-09-02 | 7/14/2005 | IM | 1 | M244V (∼80) | M244V (79.31), H396R (6.75), L298V (3.75), L364I (3.28) | N.A. | Loss of complete hematologic response |
| CP-09-03 | 9/3/2007 | DAS | 2 | M244V (∼70), T315A (∼60) | M244V (73.36), T315A (57.53), F425S (2.18), T406I (1.75) | N.A. | Complete hematologic response but no cytogenetic response |
| AP-10-01 | 3/7/2005 | IM | 1 | E355G (∼50) | E355G (43.75), L341P (21.75), F496L (19.63), L428L (11.01), T315I (10.24), Y456Y (4.81) | N.A. | Progression from CP to AP after 9 mo on IM |
| AP-10-02 | 4/11/2005 | DAS | 2 | T315I (∼50) | T315I (42.60), F317L (1.25) | T315I (42.60), F317L (1.25) | Progression to MBC |
| MBC-11-01 | 4/12/2010 | IM | 1 | M351T (∼100), L248V (∼30) | N.D. | N.D. | Loss of complete hematologic response after 6 mo on IM |
| MBC-11-02 | 8/23/2010 | DAS | 2 | M351T (∼100), F317L (∼70), L248V (∼20) | M351T (100.00), F317L(ttc>tta)(65.52), L248V (19.45), del(248-274) (9.52), F317L(ttc>ctc)(8.52), V299L (1.99) | M351T+F317L(ttc>tta) (52.60), M351T (10.30), M351T+L248V (9.29), M351T+F317L(ttc>tta)+L248V (8.78), M351T+F317L(ttc>ctc) (6.33), M351T+del(248-274)(4.77), M351T+F317L(ttc>tta)+del(248-274)(4.14), M351T+V299L (1.41), M351T+L248V+F317L(ttc>ctc) (1.19), M351T+del(248-274)+F317L(ttc>ctc) (0.61), M351T+F317L(ttc>ctc)+V299L (0.39), M351T+L248V+V299L (0.19) | No hematologic response |
| MBC-12-01 | 3/5/2012 | IM | 1 | F359V (∼70) | F359V (63.24), L387M (4.18), M351T (3.42), V379I (1.62) | F359V (60.26), L387M (2.47), M351T (2.45), F359V+L387M (1.61), V379I (1.12), F359V+M351T (0.87), F359V+V379I (0.50), M351T+L387M (0.10) | Loss of complete cytogenetic response after 12 mo on IM |
| MBC-12-02 | 9/24/2012 | DAS | 2 | L387M (∼60), T315A (∼50), F359V (∼20) | L387M (57.43), T315A (57.19), F359V (16.24), T315I (8.22), F317V (3.98), F317L (1.15) | L387M+T315A (55.99), F359V+T315I (8.06), F359V (4.37), F359V+F317V (3.63), T315A (1.20), L387M+F317L (0.97), F317V (0.19), F359V+F317L (0.18), L387M+T315I (0.16), L387M+F317V (0.16), L387M (0.15) | Loss of complete hematologic response |
| MBC-13-01 | 5/28/2010 | DAS | 2 | T315A (∼100) | T315A (73.75), V299L (8.19) | T315A (72.40), V299L (6.84), T315A +V299L (1.35) | Loss of complete hematologic response after 6 mo on DAS |
| MBC-13-02 | 12/9/2010 | NIL | 3 | T315A (∼100), E255V (∼70), G250E (∼15) | T315A (92.87), E255V (69.74), G250E (12.22), E255K (1.03) | T315A+E255V (65.07), T315A (15.72), T315A+G250E (10.44), E255V (3.73), T315A+E255V+G250E (0.94), G250E (0.84), T315A+E255K (0.70), E255K (0.33) | No hematologic response |
| LBC-14-01 | 12/20/2011 | IM | 1 | G250E (∼40), E255V (∼20) | G250E (34.28), E255V (15.05), E255K (2.34), Y253F (1.10) | G250E (32.91), E255V (14.09), E255K (2.13), Y253F (0.90), G250E+E255V (0.96), G250E+E255K (0.21), G250E+Y253F (0.20) | Progression to lymphoid bast crisis after 32 mo on IM |
| LBC-14-02 | 2/8/2012 | DAS | 2 | T315I (∼30) | T315I (28.92) | T315I (28.92) | No hematologic response |
| LBC-15-01 | 5/26/2011 | IM | 1 | Y253H (∼100) | Y253H (99.88) | Y253H (99.88) | Hematologic relapse |
| LBC-15-02 | 12/5/2011 | DAS | 2 | Y253H (∼50), F317L (∼50) | Y253H (54.90), F317L (54.40) | Y253H+F317L (43.00), Y253H (11.90), F317L (11.40) | Hematologic relapse |
| LBC-16-01 | 3/14/2005 | IM | 1 | E255K (∼100) | E255K (98.84) | E255K (98.84) | Progression to LBC after 9 mo on IM |
| LBC-16-02 | 4/19/2005 | DAS | 2 | E255K (∼100), T315I (∼100) | E255K (99.84), T315I (99.48), L273S (1.30) | E255K+T315I (97.83), E255K (0.71), E255K+T315I+L273S (1.30), T315I (0.35) | No hematologic response |
| LBC-16-03 | 5/23/2005 | DAS | 2 | E255K (∼100), T315I (∼100) | E255K (99.53), T315I (99.53) | E255K+T315I (99.53) | No hematologic response |
| LBC-17-01 | 11/29/2010 | IM | 1 | L387M (∼30) | L387M (34.12) | L387M (28.18) | Loss of complete hematologic response after 6 mo on IM |
| LBC-17-02 | 2/27/2012 | DAS | 2 | L387M (∼100), T315I (∼50), M318V (∼50), F317L (∼50), Y320N (∼50) | L387M (96.33), T315I (51.46), M318V (51.19), F317L (45.21), Y320N (44.79) | L387M+T315I+M318V (47.90), L387M+F317L+Y320N (42.21), L387M (2.63), T315I+M318V (1.82), F317L+Y320N (1.37), L387M+F317L (1.10), L387M+T315I+M318V+Y320N (0.80), L387M+M318V (0.50), L387M+T315I+F317L (0.36), L387M+Y320N (0.25), L387M+T315I (0.25), L387M+T315I+M318V+F317L (0.17), L387M+T315I+Y320N (0.16) | Loss of cytogenetic and hematologic response |
| LBC-18-01 | 11/11/2007 | IM | 1 | F359V (∼60) | F359V (57.89) | F359V (57.89) | Progression to LBC after 3 mo on IM |
| LBC-18-02 | 1/17/2008 | DAS | 2 | None | F317L (8.48), F317I (1.02), F359V (1.02) | F317L (8.48), F317I+F359V (1.02) | Complete hematologic response, partial cytogenetic response |
| LBC-18-03 | 2/12/2008 | DAS | 2 | F359V (∼100), F317I (∼100) | F317I (92.35), F359V (90.11), F317L (4.25) | F359V+F317I (88.01), F317I (4.34), F317L (3.12), F359V+F317L (1.13), F359V (0.97) | Loss of complete hematologic response |
| ALL-19-01 | 9/27/2005 | IM | 1 | Y253H (∼100) | Y253H (99.79) | Y253H (99.79) | Hematologic relapse after 6 mo on IM |
| ALL-19-02 | 1/3/2006 | DAS | 2 | None | P465L (2.78), I432I (1.60), T277I (1.56), E352V (1.41), A474A (1.15) | N.A. | Complete hematologic and cytogenetic response, molecularly detectable disease |
| ALL-19-03 | 3/2/2006 | DAS | 2 | None | A399V (1.58) | A399V (1.58) | Complete hematologic and cytogenetic response, molecularly detectable disease |
| ALL-19-04 | 6/15/2006 | DAS | 2 | Y253H (∼100), T315I (∼50) | Y253H (99.70), T315I (40.29), N336S (5.39), W405R (1.89) | N.A. | Hematologic relapse |
| ALL-20-01 | 1/11/2005 | IM | 1 | M351T (∼100) | M351T (99.91) | M351T (99.91) | Hematologic relapse after 12 mo on IM |
| ALL-20-02 | 3/12/2005 | DAS | 2 | None | L370L (5.45), I432I (2.65) | N.A. | Complete hematologic and cytogenetic response, molecularly detectable disease |
| ALL-20-03 | 1/16/2006 | DAS | 2 | M351T (∼100), F317L (∼50) | M351T (99.77), F317L (53.27) | M351T (46.50), M351T+F317L (53.27) | Hematologic relapse |
| ALL-20-04 | 4/7/2006 | DAS | 2 | M351T (∼100), F317L (∼100) | M351T (95.46), F317L (85.32), A399T (5.64), Y353H (1.00) | M351T+F317L (85.32), M351T+A399T (5.64), M351T (3.50), M351T+F317L+Y353H (1.00) | Progressive disease |
| ALL-21-01 | 5/30/2005 | DAS | 2 | F317L (∼100) | F317L (99.99), M237I (2.03) | F317L (97.96), F317L+M237I (2.03) | Hematologic relapse after 3 mo on DAS |
| ALL-21-02 | 10/27/2005 | NIL | 3 | F317L (∼100), Y253H (∼20) | F317L (98.59), Y253H (17.35) | F317L (81.24), F317L+Y253H (17.35) | Complete hematologic response but no cytogenetic response |
| ALL-21-03 | 1/16/2006 | NIL | 3 | F317L (∼100), Y253H (∼20) | F317L (100.00), Y253H (18.77) | F317L (81.23), F317L+Y253H (18.77) | Hematologic relapse |
| ALL-21-04 | 3/17/2006 | NIL | 3 | F317L (∼100), Y253H (∼100) | F317L (100.00), Y253H (100.00) | F317L+Y253H (100.00) | Progressive disease |
| ALL-22-01 | 12/23/2005 | IM | 1 | F359V (∼100) | F359V (99.76), M237T (2.11) | N.A. | Hematologic relapse after 26 mo on IM |
| ALL-22-02 | 1/29/2005 | DAS | 2 | F359V (∼100), T315I (∼100) | F359V (99.30), T315I (98.77), Y449Y (10.50) | N.A. | Progressive disease |
| ALL-23-01 | 9/14/2011 | DAS | 2 | E255K (∼30), T315I (∼20) | E255K (24.04), T315I (19.37), G303G (1.51) | E255K (20.88), T315I (16.21), E255K+T315I (3.16), G303G (1.51) | Hematologic relapse after 9 mo on DAS |
| ALL-23-02 | 10/27/2011 | PON | 3 | T315I (∼100) | T315I (99.78), Y312C (1.22) | T315I (98.28), T315I+Y312C (1.22) | Complete hematologic response |
| ALL-23-03 | 11/3/2011 | PON | 3 | T315I (∼100) | T315I (99.83) | T315I (99.83) | Complete hematologic response |
| ALL-23-04 | 12/15/2011 | POST-SCT, NONE | / | None | None | None | Complete hematologic and cytogenetic response, molecularly detectable disease |
| ALL-23-05 | 1/11/2012 | POST-SCT, IM | 4 | E255K (∼100) | E255K (99.88) | E255K (99.88) | Complete hematologic response but loss of cytogenetic response |
| ALL-23-06 | 1/25/2012 | PON | 5 | E255K (∼100) | E255K (99.36), S417S (2.21) | N.A. | Hematologic relapse |
| ALL-23-07 | 2/8/2012 | PON | 5 | E255K (∼30) | E255K (22.49) | E255K (22.49) | Complete hematologic response |
| ALL-23-08 | 2/15/2012 | PON | 5 | E255K (∼100) | E255K (99.88) | E255K (99.88) | Partial hematologic response |
| ALL-23-09 | 3/12/2012 | DAS | 6 | E255K (∼70), T315I (∼50) | E255K (76.10), T315I (57.35), Q252H (cag>cac)(14.19), Q252H (cag>cat)(7.49), G250E (1.05) | E255K+T315I (51.60), E255K+Q252H (cag>cac) (13.94), E255K+Q252H (cag>cat) (7.34),T315I (5.75), E255K (2.52), E255K+ G250E (0.70), Q252H (cag>cac) (0.25), G250E (0.35), Q252H (cag>cat) (0.15) | Progressive disease |
| ALL-23-10 | 3/28/2012 | PON | 7 | E255K (∼100), T315I (∼100) | E255K (99.64), T315I (98.56) | E255K+T315I (98.20), E255K (1.44), T315I (0.36) | Progressive disease |
| ALL-24-01 | 6/15/2011 | NIL | 1 | Y253H (∼30) | Y253H (27.35), P465L (1.55) | N.A. | Complete hematologic and cytogenetic response, molecularly detectable disease |
| ALL-24-02 | 7/28/2011 | IM | 2 | Y253H (∼100) | Y253H (99.99), R367L (3.62) | Y253H (96.37), Y253H+R367L (3.62) | Complete hematologic and cytogenetic response, but 1-log increase in BCR-ABL transcript levels |
| ALL-24-03 | 3/1/2012 | DAS | 3 | None | Y302S (1.62) | Y302S (1.62) | Complete hematologic and cytogenetic response, no molecular assessment performed |
| ALL-24-04 | 3/29/2012 | DAS | 3 | Y253H (∼100), T315I (∼100) | Y253H (99.10), T315I (99.10), L273L (1.09) | Y253H+T315I (98.01); Y253H+T315I+L273L (1.09) | Hematologic relapse |
| ALL-25-01 | 12/2/2011 | IM | 1 | Y253H (∼20) | Y253H (18.38) | Y253H (18.38) | Complete hematologic and cytogenetic response, molecularly detectable disease after 18 mo on IM |
| ALL-25-02 | 1/18/2012 | DAS | 2 | Y253H (∼100), T315I (∼100) | Y253H (87.69), T315I (86.16) | Y253H+T315I (80.53), Y253H (7.16), T315I (5.63) | Hematologic relapse |
| ALL-26-01 | 1/11/2012 | IM | 1 | E255K (∼60) | E255K (54.75), F359V (13.81), T315I (3.84) | N.A. | Hematologic relapse after 6 mo on IM |
| ALL-26-02 | 6/16/2012 | DAS | 2 | T315I (∼100) | T315I (99.42) | T315I (99.42) | Progressive disease |
| ALL-27-01 | 1/14/2011 | IM | 1 | T315I (∼100) | T315I (99.87) | T315I (99.87) | Complete hematologic but not cytogenetic response after 3 mo on IM |
| ALL-27-02 | 1/31/2011 | IM | 1 | T315I (∼100) | T315I (99.74) | T315I (99.74) | Stable disease |
| ALL-27-03 | 2/7/2011 | NIL | 2 | T315I (∼80) | T315I (75.55), E255K (9.70), E255V (1.53) | T315I (70.47), E255K (5.10), T315I+E255K (4.60), E255V (1.05), T315I+E255V (0.48) | Stable disease |
| ALL-27-04 | 2/21/2011 | NIL | 2 | T315I (∼60), E255K (∼30) | T315I (53.80), E255K (25.63), E255V (1.33) | T315I (46.10), E255K (18.26), T315I+E255K (7.37), E255V (1.00), T315I+E255V (0.33) | Hematologic relapse |
| ALL-28-01 | 12/5/2007 | IM | 1 | Y253H (∼50), E255K (∼20) | Y253H (56.01), E255K (14.92), T315I (8.33), Q252H (6.32), A269T (3.57), Y253F (1.37) | Y253H (52.30), E255K (14.70), T315I (5.29), Q252H (3.92), Y253H+T315I (2.93), Q252H+A269T (2.40), Y253F (1.26), Y253H+269T (0.63), A269T (0.54), Y253H+E255K (0.15), Y253F+T315I (0.11) | Hematologic relapse after 9 mo on IM |
| ALL-28-02 | 3/26/2008 | DAS | 2 | T315I (∼100) | T315I (90.96) | T315I (90.96) | Progressive disease |
| ALL-29-01 | 6/6/2012 | IM POST-SCT | 2 | T315? | T315M (30.20) | T315M (30.20) | Complete hematologic response, molecularly detectable disease |
| ALL-29-02 | 6/20/2012 | IM | 2 | T315? | T315M (22.32) | T315M (22.32) | Hematologic relapse |
| ALL-29-03 | 7/10/2012 | IM | 2 | T315? | T315M (30.28) | T315M (30.28) | Progressive disease |
| ALL-29-04 | 8/1/2012 | IM | 2 | T315? | T315M (57.28), T315I (1.09) | T315M (57.28), T315I (1.09) | Stable disease |
| ALL-29-05 | 8/22/2012 | PON | 3 | T315?, E255V (∼20) | T315M (28.61), T315I (22.93), E255V (12.40) | T315M (25.20), T315I (20.01), E255V (5.03), T315M+E255V (3.41), T315I+E255V (2.92) | Progressive disease |
| ALL-30-01 | 3/30/2010 | NIL | 1 | E255V (∼40) | E255V (34.70) | E255V (34.70) | Complete hematologic response, molecularly detectable disease after 1 mo on IM |
| ALL-30-02 | 5/12/2010 | IM | 2 | E255V (∼100) | E255V (91.90), V304A (3.91), L302R (1.61), G303W (1.61) | See Figure 3 | Complete hematologic response, molecularly detectable disease with 1-log increase in BCR-ABL transcript levels |
| ALL-30-03 | 7/19/2010 | IM | 4 | E255V (∼50), Y253H (∼50) | E255V (46.50), Y253H (39.30), E255K (1.02) | See Figure 3 | Hematologic relapse |
| ALL-30-04 | 9/7/2010 | DAS | 5 | E255V (∼100) | E255V (91.60), T315I (2.00), E255K (1.80), K262R (1.00) | See Figure 3 | Stable disease |
| ALL-30-05 | 10/5/2010 | DAS | 5 | E255V (∼50), T315I (∼30) | E255V (53.00), T315I (23.00), Q252E (14.30), E255K (2.10) | See Figure 3 | Progressive disease |
| ALL-31-01 | 4/4/2006 | IM | 1 | F317L (∼100) | F317L (99.64) | F317L (99.64) | Hematologic relapse after 5 mo on IM |
| ALL-31-02 | 6/6/2006 | DAS | 2 | D276G (∼50), F317L (∼50), T315A (∼50) | T315A (51.12), F317L (45.81), D276G (44.86) | F317L (33.45), T315A+D276G (32.00), T315A (17.87), F317L+D276G (11.11), D276G (1.25), T315A+F317L (0.75), T315A+F317L+D276G (0.50) | Hematologic relapse after transient hematologic improvement |
| ALL-31-03 | 7/14/2006 | IM | 3 | F317L (∼100) | F317L (99.76), R332R (4.17) | F317L (95.59), F317L+R332R (4.17) | Stable disease |
| ALL-31-04 | 8/23/2006 | IM | 3 | T315A (∼100), G250E (∼100) | T315A (100.00), G250E (90.48) | T315A+G250E (90.48), T315A (9.52) | Progressive disease |
| ALL-31-05 | 9/26/2006 | NIL | 4 | T315A (∼100), G250E (∼100) | T315A (99.83), G250E (99.83) | T315A+G250E (99.83) | Progressive disease |
| ALL-31-06 | 10/24/2006 | NIL | 4 | T315A (∼100), G250E (∼60), D276G (∼30), Y253H (∼30) | T315A (99.96), G250E (67.93), D276G (28.89), Y253H (27.21), Q252E (1.49) | T315A+G250E (65.82), T315A+Y253H+D276G (26.02), T315A (3.76), T315A+G250E+D276G (2.11), T315A+Q252E (0.78), T315A+Y253H (0.48), T315A+Y253H+D276G+Q252E (0.48), T315A+D276G (0.28), T315A+Y253H+Q252E (0.23) | Progressive disease |
| ALL-32-01 | 1/6/2012 | IM | 2 | Y253H (∼100) | Y253H (99.79) | Y253H (99.79) | Hematologic relapse |
| ALL-32-02 | 4/12/2012 | DAS | 3 | None | None | None | Complete hematologic and cytogenetic response, molecularly detectable disease |
| ALL-32-03 | 8/8/2012 | DAS | 3 | None | Y253H (2.49), T315I (1.19) | Y253H (1.30), Y253H+T315I (1.19) | Complete hematologic response, 2-log increase in BCR-ABL transcript levels |
| ALL-32-04 | 9/17/2012 | DAS | 3 | Y253H (∼100), T315I (∼60), F317L(ttc>tta) (∼20) | Y253H (100.00), T315I (79.11), F317L(ttc>tta)(15.70), F317L(ttc>ctc)(4.04) | Y253H+T315I ((78.77), Y253H+ F317L(ttc>tta)(15.36), Y253H+ F317L(ttc>ctc)(4.04), Y253H (1.49), Y253H+T315I+F317L(ttc>tta)(0.34) | Loss of cytogenetic response |
| ALL-33-01 | 3/27/2005 | IM | 1 | G250E (∼100) | G250E (99.50) | G250E (99.50) | Hematologic relapse |
| ALL-33-02 | 9/5/2005 | DAS | 2 | G250E (∼100), F317L (∼70) | N.D. | N.D. | Hematologic relapse after a 5-mo complete hematologic response |
| ALL-33-03 | 12/1/2005 | NIL | 3 | G250E (∼100), F317L (∼50), Y253H (∼30) | G250E (99.99), F317L(ttc>tta)(43.63), Y253H (26.36), V299L (4.84), L248R (1.89), F317L(ttc>ctc)(1.01) | G250E (35.54), G250E+F317L(ttc>tta) (31.90), G250E+Y253H (14.86), G250E+F317L(ttc>tta)+Y253H (9.84), G250E+V299L (2.72), G250E+L248R (1.13), G250E+Y253H+V299L (0.99), G250E+F317L(ttc>tta)+V299L (0.77), G250E+F317L(ttc>tta)+L248R (0.76), G250E+F317L(ttc>ctc) (0.70), G250E+F317L(ttc>tta)+V299L+Y253H (0.36), G250E+F317L(ttc>ctc)+Y253H (0.31) | Progressive disease |
| Code . | Date . | TKI . | Line . | Mutations by SS . | Mutations by UDS* . | Estimated mutated populations by UDS† . | Disease status and response . |
|---|---|---|---|---|---|---|---|
| CP-01-01 | 2/29/2012 | DAS | 2 | H396R (∼50), F317L (∼30) | H396R (55.05), F317L (28.23) | H396R (43.99), F317L (17.17), H396R+F317L (11.06) | Complete cytogenetic response but no molecular response after 6 mo on DAS |
| CP-01-02 | 5/2/2012 | DAS | 2 | F317L (∼70), H396R (∼20) | F317L (63.07), H396R (15.74), T315I (5.42) | F317L (55.47),H396R (7.60), H396R+F317L (7.38), T315I (4.44), H396R+T315I (0.76), F317L+T315I (0.22) | Complete hematologic response, cytogenetic response not assessed |
| CP-01-03 | 7/7/2012 | NIL | 3 | T315I (∼100) | T315I (99.28) | T315I (99.28) | Complete hematologic response, no cytogenetic response |
| CP-02-01 | 3/4/2008 | IM | 1 | F359V (∼20) | F359V (17.33) | F359V (17.33) | Loss of complete hematologic response after 5 mo on IM |
| CP-02-02 | 4/2/2008 | DAS | 2 | T315I (∼100) | T315I (94.80) | T315I (94.80) | Progression to LBC |
| CP-03-01 | 3/7/2005 | IM | 1 | G250E (∼100) | G250E (93.72), F317L (1.78) | G250E (92.20), G250E+F317L (1.52), F317L (0.26) | Minor cytogenetic response after 12 mo on IM |
| CP-03-02 | 9/14/2005 | DAS | 2 | G250E (∼70), F317L (∼20) | G250E (74.71), F317L (22.51) | G250E (62.00), G250E+F317L (12.71), F317L (9.80) | Minor cytogenetic response |
| CP-03-03 | 11/17/2005 | DAS | 2 | G250E (∼70), F317L (∼30) | G250E (60.73), F317L (27.06) | G250E (46.44), G250E+F317L (14.29), F317L (12.77) | Not available |
| CP-03-04 | 2/13/2006 | DAS | 2 | G250E (∼50), F317L (∼40) | G250E (45.47), F317L (37.49), H295H (4.91), C330C (1.48) | G250E (30.46), F317L (20.40), G250E+F317L (12.47), F317L+H295H (2.14), G250E+F317L+H295H (1.19), H295H (0.89), F317L+C330C (0.82), G250E+H295H (0.69), G250E+F317L+C330C (0.47), G250E+C330C (0.19) | Complete hematologic response, no cytogenetic response |
| CP-03-05 | 5/15/2006 | NIL | 3 | G250E (∼100), E255E (∼100) | G250E (87.17), E255E (85.78), F317L (10.44) | G250E+E255E (77.90), G250E+F317L+E255E (7.66), F317L (2.56), G250E (1.61), F317L+E255E (0.22) | Complete hematologic response, no cytogenetic response |
| CP-04-01 | 10/20/2005 | IM | 1 | L384M (∼100) | L384M (87.04), E255V (15.14) | N.A. | Loss of complete cytogenetic response after 24 mo on IM |
| CP-04-02 | 12/22/2005 | NIL | 2 | L384M (∼70), E255V (∼30) | L384M (68.33), E255V (32.02), M351I (2.64) | N.A. | Loss of complete hematologic response |
| CP-04-03 | 1/24/2006 | NIL | 2 | E255V (∼100) | E255V (80.71), L384M (14.40) | N.A. | No hematologic response |
| CP-05-01 | 1/20/2005 | IM | 1 | G250E (∼100) | G250E (99.51) | G250E (99.51) | Loss of complete cytogenetic response after 36 mo on IM |
| CP-05-02 | 3/23/2005 | DAS | 2 | F317L (∼30), G250E (∼30) | F317L (24.93), G250E (22.89), C305C (11.70), K274E (10.38) | G250E (16.52), F317L (15.06), C305C (9.30), G250E+F317L (4.30), K274E (4.09) F317L+K274E (3.70), G250E+K274E (1.04), C305C+F317L (0.97), C305+CK274E (0.91), G250E+F317L+K274E (0.51), G250E+C305C+F317L (0.39), G250E+C305C+K274E (0.13) | Not available |
| CP-05-03 | 4/20/2005 | DAS | 2 | F317L (∼100) | F317L (99.50) | F317L (99.50) | Complete hematologic response, no cytogenetic response |
| CP-06-01 | 4/19/2005 | IM | 1 | H396R (∼100) | H396R (99.63), A413A (1.71), K247N (1.11) | N.A. | Partial cytogenetic response after 18 mo on IM |
| CP-06-02 | 5/17/2005 | DAS | 2 | None | H396R (16.07), F317L (7.43) | H396R (16.07), F317L (7.43) | Complete cytogenetic response (= 0/200 Ph+ by FISH) |
| CP-06-03 | 6/14/2005 | DAS | 2 | F317L (∼20) | F317L (20.86), H396R (3.54) | F317L (20.20), H396R (2.88), F317L+H396R (0.66) | Loss of complete cytogenetic response (= 30/200 Ph+ by FISH) |
| CP-07-01 | 3/22/2007 | IM | 1 | None | A433A (1.48), P408P (1.42), K378R (1.32) | A433A (1.48), P408P (1.42), K378R (1.32) | No cytogenetic response after 12 mo on IM |
| CP-07-02 | 9/8/2009 | NIL | 2 | T315I (∼30) | T315I (25.99), M351T (5.93), T345T (6.37), R332R (5.91) | T315I (20.47), T345T (6.15), R332R (5.75), T315I+M351T (5.30), M351T (0.47), T315I+T345T (0.22), M351T+R332R (0.16) | No cytogenetic response |
| CP-07-03 | 3/4/2010 | NIL | 2 | T315I (∼70) | T315I (65.85), Y253H (16.65), W235R (3.77), F497L (3.14), T406I (2.43), Q477Q (2.37), F486S (2.28), D363N (1.47) | N.A. | No cytogenetic response; transplanted 6 mo later |
| CP-08-01 | 6/22/2010 | IM | 1 | M351T (∼100), E499E (∼100) | M351T (99.84), E499E (99.84) | N.A. | No cytogenetic response after 12 mo on IM |
| CP-08-02 | 4/26/2012 | NIL | 2 | Y253H (∼100), E499E (∼100) | Y253H (95.64), E499E (99.67), M351T (3.20) | N.A. | No cytogenetic response |
| CP-09-01 | 6/22/2004 | IM | 1 | M244V (∼20) | M244V (19.4), H396R (2.88), L298V (1.91), L364I (1.64) | N.A. | No cytogenetic response after 15 mo on IM |
| CP-09-02 | 7/14/2005 | IM | 1 | M244V (∼80) | M244V (79.31), H396R (6.75), L298V (3.75), L364I (3.28) | N.A. | Loss of complete hematologic response |
| CP-09-03 | 9/3/2007 | DAS | 2 | M244V (∼70), T315A (∼60) | M244V (73.36), T315A (57.53), F425S (2.18), T406I (1.75) | N.A. | Complete hematologic response but no cytogenetic response |
| AP-10-01 | 3/7/2005 | IM | 1 | E355G (∼50) | E355G (43.75), L341P (21.75), F496L (19.63), L428L (11.01), T315I (10.24), Y456Y (4.81) | N.A. | Progression from CP to AP after 9 mo on IM |
| AP-10-02 | 4/11/2005 | DAS | 2 | T315I (∼50) | T315I (42.60), F317L (1.25) | T315I (42.60), F317L (1.25) | Progression to MBC |
| MBC-11-01 | 4/12/2010 | IM | 1 | M351T (∼100), L248V (∼30) | N.D. | N.D. | Loss of complete hematologic response after 6 mo on IM |
| MBC-11-02 | 8/23/2010 | DAS | 2 | M351T (∼100), F317L (∼70), L248V (∼20) | M351T (100.00), F317L(ttc>tta)(65.52), L248V (19.45), del(248-274) (9.52), F317L(ttc>ctc)(8.52), V299L (1.99) | M351T+F317L(ttc>tta) (52.60), M351T (10.30), M351T+L248V (9.29), M351T+F317L(ttc>tta)+L248V (8.78), M351T+F317L(ttc>ctc) (6.33), M351T+del(248-274)(4.77), M351T+F317L(ttc>tta)+del(248-274)(4.14), M351T+V299L (1.41), M351T+L248V+F317L(ttc>ctc) (1.19), M351T+del(248-274)+F317L(ttc>ctc) (0.61), M351T+F317L(ttc>ctc)+V299L (0.39), M351T+L248V+V299L (0.19) | No hematologic response |
| MBC-12-01 | 3/5/2012 | IM | 1 | F359V (∼70) | F359V (63.24), L387M (4.18), M351T (3.42), V379I (1.62) | F359V (60.26), L387M (2.47), M351T (2.45), F359V+L387M (1.61), V379I (1.12), F359V+M351T (0.87), F359V+V379I (0.50), M351T+L387M (0.10) | Loss of complete cytogenetic response after 12 mo on IM |
| MBC-12-02 | 9/24/2012 | DAS | 2 | L387M (∼60), T315A (∼50), F359V (∼20) | L387M (57.43), T315A (57.19), F359V (16.24), T315I (8.22), F317V (3.98), F317L (1.15) | L387M+T315A (55.99), F359V+T315I (8.06), F359V (4.37), F359V+F317V (3.63), T315A (1.20), L387M+F317L (0.97), F317V (0.19), F359V+F317L (0.18), L387M+T315I (0.16), L387M+F317V (0.16), L387M (0.15) | Loss of complete hematologic response |
| MBC-13-01 | 5/28/2010 | DAS | 2 | T315A (∼100) | T315A (73.75), V299L (8.19) | T315A (72.40), V299L (6.84), T315A +V299L (1.35) | Loss of complete hematologic response after 6 mo on DAS |
| MBC-13-02 | 12/9/2010 | NIL | 3 | T315A (∼100), E255V (∼70), G250E (∼15) | T315A (92.87), E255V (69.74), G250E (12.22), E255K (1.03) | T315A+E255V (65.07), T315A (15.72), T315A+G250E (10.44), E255V (3.73), T315A+E255V+G250E (0.94), G250E (0.84), T315A+E255K (0.70), E255K (0.33) | No hematologic response |
| LBC-14-01 | 12/20/2011 | IM | 1 | G250E (∼40), E255V (∼20) | G250E (34.28), E255V (15.05), E255K (2.34), Y253F (1.10) | G250E (32.91), E255V (14.09), E255K (2.13), Y253F (0.90), G250E+E255V (0.96), G250E+E255K (0.21), G250E+Y253F (0.20) | Progression to lymphoid bast crisis after 32 mo on IM |
| LBC-14-02 | 2/8/2012 | DAS | 2 | T315I (∼30) | T315I (28.92) | T315I (28.92) | No hematologic response |
| LBC-15-01 | 5/26/2011 | IM | 1 | Y253H (∼100) | Y253H (99.88) | Y253H (99.88) | Hematologic relapse |
| LBC-15-02 | 12/5/2011 | DAS | 2 | Y253H (∼50), F317L (∼50) | Y253H (54.90), F317L (54.40) | Y253H+F317L (43.00), Y253H (11.90), F317L (11.40) | Hematologic relapse |
| LBC-16-01 | 3/14/2005 | IM | 1 | E255K (∼100) | E255K (98.84) | E255K (98.84) | Progression to LBC after 9 mo on IM |
| LBC-16-02 | 4/19/2005 | DAS | 2 | E255K (∼100), T315I (∼100) | E255K (99.84), T315I (99.48), L273S (1.30) | E255K+T315I (97.83), E255K (0.71), E255K+T315I+L273S (1.30), T315I (0.35) | No hematologic response |
| LBC-16-03 | 5/23/2005 | DAS | 2 | E255K (∼100), T315I (∼100) | E255K (99.53), T315I (99.53) | E255K+T315I (99.53) | No hematologic response |
| LBC-17-01 | 11/29/2010 | IM | 1 | L387M (∼30) | L387M (34.12) | L387M (28.18) | Loss of complete hematologic response after 6 mo on IM |
| LBC-17-02 | 2/27/2012 | DAS | 2 | L387M (∼100), T315I (∼50), M318V (∼50), F317L (∼50), Y320N (∼50) | L387M (96.33), T315I (51.46), M318V (51.19), F317L (45.21), Y320N (44.79) | L387M+T315I+M318V (47.90), L387M+F317L+Y320N (42.21), L387M (2.63), T315I+M318V (1.82), F317L+Y320N (1.37), L387M+F317L (1.10), L387M+T315I+M318V+Y320N (0.80), L387M+M318V (0.50), L387M+T315I+F317L (0.36), L387M+Y320N (0.25), L387M+T315I (0.25), L387M+T315I+M318V+F317L (0.17), L387M+T315I+Y320N (0.16) | Loss of cytogenetic and hematologic response |
| LBC-18-01 | 11/11/2007 | IM | 1 | F359V (∼60) | F359V (57.89) | F359V (57.89) | Progression to LBC after 3 mo on IM |
| LBC-18-02 | 1/17/2008 | DAS | 2 | None | F317L (8.48), F317I (1.02), F359V (1.02) | F317L (8.48), F317I+F359V (1.02) | Complete hematologic response, partial cytogenetic response |
| LBC-18-03 | 2/12/2008 | DAS | 2 | F359V (∼100), F317I (∼100) | F317I (92.35), F359V (90.11), F317L (4.25) | F359V+F317I (88.01), F317I (4.34), F317L (3.12), F359V+F317L (1.13), F359V (0.97) | Loss of complete hematologic response |
| ALL-19-01 | 9/27/2005 | IM | 1 | Y253H (∼100) | Y253H (99.79) | Y253H (99.79) | Hematologic relapse after 6 mo on IM |
| ALL-19-02 | 1/3/2006 | DAS | 2 | None | P465L (2.78), I432I (1.60), T277I (1.56), E352V (1.41), A474A (1.15) | N.A. | Complete hematologic and cytogenetic response, molecularly detectable disease |
| ALL-19-03 | 3/2/2006 | DAS | 2 | None | A399V (1.58) | A399V (1.58) | Complete hematologic and cytogenetic response, molecularly detectable disease |
| ALL-19-04 | 6/15/2006 | DAS | 2 | Y253H (∼100), T315I (∼50) | Y253H (99.70), T315I (40.29), N336S (5.39), W405R (1.89) | N.A. | Hematologic relapse |
| ALL-20-01 | 1/11/2005 | IM | 1 | M351T (∼100) | M351T (99.91) | M351T (99.91) | Hematologic relapse after 12 mo on IM |
| ALL-20-02 | 3/12/2005 | DAS | 2 | None | L370L (5.45), I432I (2.65) | N.A. | Complete hematologic and cytogenetic response, molecularly detectable disease |
| ALL-20-03 | 1/16/2006 | DAS | 2 | M351T (∼100), F317L (∼50) | M351T (99.77), F317L (53.27) | M351T (46.50), M351T+F317L (53.27) | Hematologic relapse |
| ALL-20-04 | 4/7/2006 | DAS | 2 | M351T (∼100), F317L (∼100) | M351T (95.46), F317L (85.32), A399T (5.64), Y353H (1.00) | M351T+F317L (85.32), M351T+A399T (5.64), M351T (3.50), M351T+F317L+Y353H (1.00) | Progressive disease |
| ALL-21-01 | 5/30/2005 | DAS | 2 | F317L (∼100) | F317L (99.99), M237I (2.03) | F317L (97.96), F317L+M237I (2.03) | Hematologic relapse after 3 mo on DAS |
| ALL-21-02 | 10/27/2005 | NIL | 3 | F317L (∼100), Y253H (∼20) | F317L (98.59), Y253H (17.35) | F317L (81.24), F317L+Y253H (17.35) | Complete hematologic response but no cytogenetic response |
| ALL-21-03 | 1/16/2006 | NIL | 3 | F317L (∼100), Y253H (∼20) | F317L (100.00), Y253H (18.77) | F317L (81.23), F317L+Y253H (18.77) | Hematologic relapse |
| ALL-21-04 | 3/17/2006 | NIL | 3 | F317L (∼100), Y253H (∼100) | F317L (100.00), Y253H (100.00) | F317L+Y253H (100.00) | Progressive disease |
| ALL-22-01 | 12/23/2005 | IM | 1 | F359V (∼100) | F359V (99.76), M237T (2.11) | N.A. | Hematologic relapse after 26 mo on IM |
| ALL-22-02 | 1/29/2005 | DAS | 2 | F359V (∼100), T315I (∼100) | F359V (99.30), T315I (98.77), Y449Y (10.50) | N.A. | Progressive disease |
| ALL-23-01 | 9/14/2011 | DAS | 2 | E255K (∼30), T315I (∼20) | E255K (24.04), T315I (19.37), G303G (1.51) | E255K (20.88), T315I (16.21), E255K+T315I (3.16), G303G (1.51) | Hematologic relapse after 9 mo on DAS |
| ALL-23-02 | 10/27/2011 | PON | 3 | T315I (∼100) | T315I (99.78), Y312C (1.22) | T315I (98.28), T315I+Y312C (1.22) | Complete hematologic response |
| ALL-23-03 | 11/3/2011 | PON | 3 | T315I (∼100) | T315I (99.83) | T315I (99.83) | Complete hematologic response |
| ALL-23-04 | 12/15/2011 | POST-SCT, NONE | / | None | None | None | Complete hematologic and cytogenetic response, molecularly detectable disease |
| ALL-23-05 | 1/11/2012 | POST-SCT, IM | 4 | E255K (∼100) | E255K (99.88) | E255K (99.88) | Complete hematologic response but loss of cytogenetic response |
| ALL-23-06 | 1/25/2012 | PON | 5 | E255K (∼100) | E255K (99.36), S417S (2.21) | N.A. | Hematologic relapse |
| ALL-23-07 | 2/8/2012 | PON | 5 | E255K (∼30) | E255K (22.49) | E255K (22.49) | Complete hematologic response |
| ALL-23-08 | 2/15/2012 | PON | 5 | E255K (∼100) | E255K (99.88) | E255K (99.88) | Partial hematologic response |
| ALL-23-09 | 3/12/2012 | DAS | 6 | E255K (∼70), T315I (∼50) | E255K (76.10), T315I (57.35), Q252H (cag>cac)(14.19), Q252H (cag>cat)(7.49), G250E (1.05) | E255K+T315I (51.60), E255K+Q252H (cag>cac) (13.94), E255K+Q252H (cag>cat) (7.34),T315I (5.75), E255K (2.52), E255K+ G250E (0.70), Q252H (cag>cac) (0.25), G250E (0.35), Q252H (cag>cat) (0.15) | Progressive disease |
| ALL-23-10 | 3/28/2012 | PON | 7 | E255K (∼100), T315I (∼100) | E255K (99.64), T315I (98.56) | E255K+T315I (98.20), E255K (1.44), T315I (0.36) | Progressive disease |
| ALL-24-01 | 6/15/2011 | NIL | 1 | Y253H (∼30) | Y253H (27.35), P465L (1.55) | N.A. | Complete hematologic and cytogenetic response, molecularly detectable disease |
| ALL-24-02 | 7/28/2011 | IM | 2 | Y253H (∼100) | Y253H (99.99), R367L (3.62) | Y253H (96.37), Y253H+R367L (3.62) | Complete hematologic and cytogenetic response, but 1-log increase in BCR-ABL transcript levels |
| ALL-24-03 | 3/1/2012 | DAS | 3 | None | Y302S (1.62) | Y302S (1.62) | Complete hematologic and cytogenetic response, no molecular assessment performed |
| ALL-24-04 | 3/29/2012 | DAS | 3 | Y253H (∼100), T315I (∼100) | Y253H (99.10), T315I (99.10), L273L (1.09) | Y253H+T315I (98.01); Y253H+T315I+L273L (1.09) | Hematologic relapse |
| ALL-25-01 | 12/2/2011 | IM | 1 | Y253H (∼20) | Y253H (18.38) | Y253H (18.38) | Complete hematologic and cytogenetic response, molecularly detectable disease after 18 mo on IM |
| ALL-25-02 | 1/18/2012 | DAS | 2 | Y253H (∼100), T315I (∼100) | Y253H (87.69), T315I (86.16) | Y253H+T315I (80.53), Y253H (7.16), T315I (5.63) | Hematologic relapse |
| ALL-26-01 | 1/11/2012 | IM | 1 | E255K (∼60) | E255K (54.75), F359V (13.81), T315I (3.84) | N.A. | Hematologic relapse after 6 mo on IM |
| ALL-26-02 | 6/16/2012 | DAS | 2 | T315I (∼100) | T315I (99.42) | T315I (99.42) | Progressive disease |
| ALL-27-01 | 1/14/2011 | IM | 1 | T315I (∼100) | T315I (99.87) | T315I (99.87) | Complete hematologic but not cytogenetic response after 3 mo on IM |
| ALL-27-02 | 1/31/2011 | IM | 1 | T315I (∼100) | T315I (99.74) | T315I (99.74) | Stable disease |
| ALL-27-03 | 2/7/2011 | NIL | 2 | T315I (∼80) | T315I (75.55), E255K (9.70), E255V (1.53) | T315I (70.47), E255K (5.10), T315I+E255K (4.60), E255V (1.05), T315I+E255V (0.48) | Stable disease |
| ALL-27-04 | 2/21/2011 | NIL | 2 | T315I (∼60), E255K (∼30) | T315I (53.80), E255K (25.63), E255V (1.33) | T315I (46.10), E255K (18.26), T315I+E255K (7.37), E255V (1.00), T315I+E255V (0.33) | Hematologic relapse |
| ALL-28-01 | 12/5/2007 | IM | 1 | Y253H (∼50), E255K (∼20) | Y253H (56.01), E255K (14.92), T315I (8.33), Q252H (6.32), A269T (3.57), Y253F (1.37) | Y253H (52.30), E255K (14.70), T315I (5.29), Q252H (3.92), Y253H+T315I (2.93), Q252H+A269T (2.40), Y253F (1.26), Y253H+269T (0.63), A269T (0.54), Y253H+E255K (0.15), Y253F+T315I (0.11) | Hematologic relapse after 9 mo on IM |
| ALL-28-02 | 3/26/2008 | DAS | 2 | T315I (∼100) | T315I (90.96) | T315I (90.96) | Progressive disease |
| ALL-29-01 | 6/6/2012 | IM POST-SCT | 2 | T315? | T315M (30.20) | T315M (30.20) | Complete hematologic response, molecularly detectable disease |
| ALL-29-02 | 6/20/2012 | IM | 2 | T315? | T315M (22.32) | T315M (22.32) | Hematologic relapse |
| ALL-29-03 | 7/10/2012 | IM | 2 | T315? | T315M (30.28) | T315M (30.28) | Progressive disease |
| ALL-29-04 | 8/1/2012 | IM | 2 | T315? | T315M (57.28), T315I (1.09) | T315M (57.28), T315I (1.09) | Stable disease |
| ALL-29-05 | 8/22/2012 | PON | 3 | T315?, E255V (∼20) | T315M (28.61), T315I (22.93), E255V (12.40) | T315M (25.20), T315I (20.01), E255V (5.03), T315M+E255V (3.41), T315I+E255V (2.92) | Progressive disease |
| ALL-30-01 | 3/30/2010 | NIL | 1 | E255V (∼40) | E255V (34.70) | E255V (34.70) | Complete hematologic response, molecularly detectable disease after 1 mo on IM |
| ALL-30-02 | 5/12/2010 | IM | 2 | E255V (∼100) | E255V (91.90), V304A (3.91), L302R (1.61), G303W (1.61) | See Figure 3 | Complete hematologic response, molecularly detectable disease with 1-log increase in BCR-ABL transcript levels |
| ALL-30-03 | 7/19/2010 | IM | 4 | E255V (∼50), Y253H (∼50) | E255V (46.50), Y253H (39.30), E255K (1.02) | See Figure 3 | Hematologic relapse |
| ALL-30-04 | 9/7/2010 | DAS | 5 | E255V (∼100) | E255V (91.60), T315I (2.00), E255K (1.80), K262R (1.00) | See Figure 3 | Stable disease |
| ALL-30-05 | 10/5/2010 | DAS | 5 | E255V (∼50), T315I (∼30) | E255V (53.00), T315I (23.00), Q252E (14.30), E255K (2.10) | See Figure 3 | Progressive disease |
| ALL-31-01 | 4/4/2006 | IM | 1 | F317L (∼100) | F317L (99.64) | F317L (99.64) | Hematologic relapse after 5 mo on IM |
| ALL-31-02 | 6/6/2006 | DAS | 2 | D276G (∼50), F317L (∼50), T315A (∼50) | T315A (51.12), F317L (45.81), D276G (44.86) | F317L (33.45), T315A+D276G (32.00), T315A (17.87), F317L+D276G (11.11), D276G (1.25), T315A+F317L (0.75), T315A+F317L+D276G (0.50) | Hematologic relapse after transient hematologic improvement |
| ALL-31-03 | 7/14/2006 | IM | 3 | F317L (∼100) | F317L (99.76), R332R (4.17) | F317L (95.59), F317L+R332R (4.17) | Stable disease |
| ALL-31-04 | 8/23/2006 | IM | 3 | T315A (∼100), G250E (∼100) | T315A (100.00), G250E (90.48) | T315A+G250E (90.48), T315A (9.52) | Progressive disease |
| ALL-31-05 | 9/26/2006 | NIL | 4 | T315A (∼100), G250E (∼100) | T315A (99.83), G250E (99.83) | T315A+G250E (99.83) | Progressive disease |
| ALL-31-06 | 10/24/2006 | NIL | 4 | T315A (∼100), G250E (∼60), D276G (∼30), Y253H (∼30) | T315A (99.96), G250E (67.93), D276G (28.89), Y253H (27.21), Q252E (1.49) | T315A+G250E (65.82), T315A+Y253H+D276G (26.02), T315A (3.76), T315A+G250E+D276G (2.11), T315A+Q252E (0.78), T315A+Y253H (0.48), T315A+Y253H+D276G+Q252E (0.48), T315A+D276G (0.28), T315A+Y253H+Q252E (0.23) | Progressive disease |
| ALL-32-01 | 1/6/2012 | IM | 2 | Y253H (∼100) | Y253H (99.79) | Y253H (99.79) | Hematologic relapse |
| ALL-32-02 | 4/12/2012 | DAS | 3 | None | None | None | Complete hematologic and cytogenetic response, molecularly detectable disease |
| ALL-32-03 | 8/8/2012 | DAS | 3 | None | Y253H (2.49), T315I (1.19) | Y253H (1.30), Y253H+T315I (1.19) | Complete hematologic response, 2-log increase in BCR-ABL transcript levels |
| ALL-32-04 | 9/17/2012 | DAS | 3 | Y253H (∼100), T315I (∼60), F317L(ttc>tta) (∼20) | Y253H (100.00), T315I (79.11), F317L(ttc>tta)(15.70), F317L(ttc>ctc)(4.04) | Y253H+T315I ((78.77), Y253H+ F317L(ttc>tta)(15.36), Y253H+ F317L(ttc>ctc)(4.04), Y253H (1.49), Y253H+T315I+F317L(ttc>tta)(0.34) | Loss of cytogenetic response |
| ALL-33-01 | 3/27/2005 | IM | 1 | G250E (∼100) | G250E (99.50) | G250E (99.50) | Hematologic relapse |
| ALL-33-02 | 9/5/2005 | DAS | 2 | G250E (∼100), F317L (∼70) | N.D. | N.D. | Hematologic relapse after a 5-mo complete hematologic response |
| ALL-33-03 | 12/1/2005 | NIL | 3 | G250E (∼100), F317L (∼50), Y253H (∼30) | G250E (99.99), F317L(ttc>tta)(43.63), Y253H (26.36), V299L (4.84), L248R (1.89), F317L(ttc>ctc)(1.01) | G250E (35.54), G250E+F317L(ttc>tta) (31.90), G250E+Y253H (14.86), G250E+F317L(ttc>tta)+Y253H (9.84), G250E+V299L (2.72), G250E+L248R (1.13), G250E+Y253H+V299L (0.99), G250E+F317L(ttc>tta)+V299L (0.77), G250E+F317L(ttc>tta)+L248R (0.76), G250E+F317L(ttc>ctc) (0.70), G250E+F317L(ttc>tta)+V299L+Y253H (0.36), G250E+F317L(ttc>ctc)+Y253H (0.31) | Progressive disease |
For SS results, mutation-relative abundance was assessed on the basis of variant peak height. In the TKI column, the TKI being administered at the time of analysis is indicated. In the Line column, the number of different lines of TKI therapy that had been administered to the patient is indicated. Disease status and response at each time point are also detailed. Response definitions as in Baccarani et al14 and Vignetti et al.23
In patient ALL-29, “T315?” denotes that 2 overlapping peaks at adjacent positions (c/t at 1091 and t/g at 1092) of codon 315 were identified in the SS chromatogram and the resulting amino acid substitution(s) could not be resolved (see supplemental Figure 9). In patients MBC-11, ALL-23, ALL-32, and ALL-33, the same amino acid changes were found to result from different nucleotide substitutions at the same codons (specified in parentheses). N.A. indicates that clonal analysis could not be possible because of multiple mutations located >450 bp apart. N.D. indicates that amplification with fusion primers was unsuccessful and the sample could not be analyzed with UDS.
ALL, Ph+ acute lymphoblastic leukemia; AP, accelerated phase; CP, chronic phase; DAS, dasatinib; FISH, fluorescence in situ hybridization; IM, imatinib; LBC, lymphoid blast crisis; MBC, myeloid blast crisis; N.A., not assessable; N.D., not done; NIL, nilotinib; PON, ponatinib; SCT, stem cell transplantation.
Cutoff set at variants ≥1%, see “Materials and methods” for details.
Percentage calculated after manual visual inspection of nucleotide sequences at the specific positions where the variants ≥1% were identified.