Details on patients with detection of kinase domain mutations
Patient no. . | Disease phase . | Therapy prior to imatinib . | Karyotype . | Mutation by ASO-PCR . | Ct mut . | Positive reactions, no./total . | Sequencing . | Best response . | Follow-up sequencing/disease status . | Last follow-up/disease status . |
|---|---|---|---|---|---|---|---|---|---|---|
| 7 | AP | IFN | 46,XY,t(9,22)[18]; 47,XY,t(9;22), +der(22)[6];47, XY,+8[1] | T3151 | 45.8 | 1/6 | WT | CHR | WT day +42/PHR; WT day +107/PHR;WT day +785/CHR | Alive in CHR day +1591 |
| 13 | AP | HU | 46,XY,t(9;22)[24]/47,XY,t(9;22), +der(22)[1] | Q252H | 35.6-40.4 | 3/6 | WT | MCR (20% Ph+) | Q252H day +176/MCR; Q252H+F359V day +325/MCR | Alive in MCR day +1087 |
| 17 | AP | IFN, HU | 46,XY,t(9;22)(q34; q11)[25] | T3151 | 46.9 | 1/6 | WT | PHR | WT day + 80/PHR; WT day+270/PHR; WT day +444/hematologic relapse | Hematologic relapse day + 531; lost to follow-up |
| 25 | AP | HU | 46,XX,add(6)(p25), t(9;22)(q34;q11) [20] | T3151 | 46.7 | 1/6 | WT | CHR | E255K+M351T day +365/CHR | Allogeneic transplant day +512 for lack of MCR |
| 29 | AP | HU, IFN | 45X-Y,t(9;22) (q34;q11) | Y253H | 40.2 | 1/6 | WT | mCR (52% Ph+) | WT day +85/CHR; WT day +267/CHR | Hematologic relapse day +452; lost to follow-up |
| 36 | AP | HU, IFN, 6-TG | 47,XY,t(9;22) (q34;q11),+der(22) [23];46,XY,t(9;22) (q34;q11)[1] | T3151 | 46.6-47.9 | 2/6 | K247R | CHR | K247R day +107/CHR | Hematologic relapse day +212; alive day +1011 |
| 41 | AP | none | 46,XX,t(9;22) (q34;q11),−der(22), +idic der (22)[12] | T3151 | 43.7 | 1/6 | WT | CCR | T3151 day +93/CCR; T3151 day +182/CCR | Alive in molecular remission day + 1009 |
| 42 | AP | IDA, ARA-C, IFN | 48,XY,+8,t(9; 22)(q34;q11),+der (22)t(9;22)(q34; q11)[8] | T3151 | 44.1-45.7 | 2/6 | WT | CCR | WT day+193/CCR | Alive in CCR day +661 |
| 45 | AP | HU, 6-TG | 44,XX,t(9;22)(q34; q11),der(14q+), t(17;18)(p11;q12?), −18,−20[23] | Y253F | 38.2 | 1/6 | WT | NA | ND | Died day +9 from sepsis |
| 46 | AP | HU, 6-TG | 46,XX,t(9;22)[10] | T3151 | 37.92-41.68 | 2/6 | WT | CHR | T3151 day +158/hematologic relapse | Hematologic relapse + 158; died day + 1350 from progressive disease |
| 48 | BC | HU, IFN | 47,XX,+8,t(9; 22)(q34;11) [16],46,XX,t(9; 22)[4] | T3151 | 45.6 | 1/6 | WT | NR | T3151 day +19/continuous blast crisis | Allogeneic transplant day + 140 for progressive disease; died from TRM |
| 55 | BC | HU | ND | F359V | 39.4-44.8 | 5/6 | F359V | NR | ND | Died day + 18 from progressive disease |
| 59 | BC | IFN, HU, 6-TG, MEL | 57,XY,+1,+4, +6,+8,t(9;22) (q34;q11),+10,+11, +16,+18,+19,+21, +der2 2[5] | Y253F | 41.2 | 1/6 | WT | NR | ND | Died day +35 from progressive disease |
| 62 | BC | IFN, HU | 45,XY,t(9;22)(q34; q11),del(10)(p13?), −13[26] | Y253H | 36.2 | 1/6 | WT | NR | WT day +92/continuous blast crisis | Died day +208 from progressive disease |
| 56 | BC | IFN, ARA-C | 46,XY,t(9;22) (q34;q11)[15] | ND | NA | NA | V2891 | NR | ND | Died day + 105 from progressive disease |
Patient no. . | Disease phase . | Therapy prior to imatinib . | Karyotype . | Mutation by ASO-PCR . | Ct mut . | Positive reactions, no./total . | Sequencing . | Best response . | Follow-up sequencing/disease status . | Last follow-up/disease status . |
|---|---|---|---|---|---|---|---|---|---|---|
| 7 | AP | IFN | 46,XY,t(9,22)[18]; 47,XY,t(9;22), +der(22)[6];47, XY,+8[1] | T3151 | 45.8 | 1/6 | WT | CHR | WT day +42/PHR; WT day +107/PHR;WT day +785/CHR | Alive in CHR day +1591 |
| 13 | AP | HU | 46,XY,t(9;22)[24]/47,XY,t(9;22), +der(22)[1] | Q252H | 35.6-40.4 | 3/6 | WT | MCR (20% Ph+) | Q252H day +176/MCR; Q252H+F359V day +325/MCR | Alive in MCR day +1087 |
| 17 | AP | IFN, HU | 46,XY,t(9;22)(q34; q11)[25] | T3151 | 46.9 | 1/6 | WT | PHR | WT day + 80/PHR; WT day+270/PHR; WT day +444/hematologic relapse | Hematologic relapse day + 531; lost to follow-up |
| 25 | AP | HU | 46,XX,add(6)(p25), t(9;22)(q34;q11) [20] | T3151 | 46.7 | 1/6 | WT | CHR | E255K+M351T day +365/CHR | Allogeneic transplant day +512 for lack of MCR |
| 29 | AP | HU, IFN | 45X-Y,t(9;22) (q34;q11) | Y253H | 40.2 | 1/6 | WT | mCR (52% Ph+) | WT day +85/CHR; WT day +267/CHR | Hematologic relapse day +452; lost to follow-up |
| 36 | AP | HU, IFN, 6-TG | 47,XY,t(9;22) (q34;q11),+der(22) [23];46,XY,t(9;22) (q34;q11)[1] | T3151 | 46.6-47.9 | 2/6 | K247R | CHR | K247R day +107/CHR | Hematologic relapse day +212; alive day +1011 |
| 41 | AP | none | 46,XX,t(9;22) (q34;q11),−der(22), +idic der (22)[12] | T3151 | 43.7 | 1/6 | WT | CCR | T3151 day +93/CCR; T3151 day +182/CCR | Alive in molecular remission day + 1009 |
| 42 | AP | IDA, ARA-C, IFN | 48,XY,+8,t(9; 22)(q34;q11),+der (22)t(9;22)(q34; q11)[8] | T3151 | 44.1-45.7 | 2/6 | WT | CCR | WT day+193/CCR | Alive in CCR day +661 |
| 45 | AP | HU, 6-TG | 44,XX,t(9;22)(q34; q11),der(14q+), t(17;18)(p11;q12?), −18,−20[23] | Y253F | 38.2 | 1/6 | WT | NA | ND | Died day +9 from sepsis |
| 46 | AP | HU, 6-TG | 46,XX,t(9;22)[10] | T3151 | 37.92-41.68 | 2/6 | WT | CHR | T3151 day +158/hematologic relapse | Hematologic relapse + 158; died day + 1350 from progressive disease |
| 48 | BC | HU, IFN | 47,XX,+8,t(9; 22)(q34;11) [16],46,XX,t(9; 22)[4] | T3151 | 45.6 | 1/6 | WT | NR | T3151 day +19/continuous blast crisis | Allogeneic transplant day + 140 for progressive disease; died from TRM |
| 55 | BC | HU | ND | F359V | 39.4-44.8 | 5/6 | F359V | NR | ND | Died day + 18 from progressive disease |
| 59 | BC | IFN, HU, 6-TG, MEL | 57,XY,+1,+4, +6,+8,t(9;22) (q34;q11),+10,+11, +16,+18,+19,+21, +der2 2[5] | Y253F | 41.2 | 1/6 | WT | NR | ND | Died day +35 from progressive disease |
| 62 | BC | IFN, HU | 45,XY,t(9;22)(q34; q11),del(10)(p13?), −13[26] | Y253H | 36.2 | 1/6 | WT | NR | WT day +92/continuous blast crisis | Died day +208 from progressive disease |
| 56 | BC | IFN, ARA-C | 46,XY,t(9;22) (q34;q11)[15] | ND | NA | NA | V2891 | NR | ND | Died day + 105 from progressive disease |
Note that K247R is a previously unreported polymorphism.
Ct mut indicates PCR cycle at which mutant signal was detected; AP, accelerated phase; IFN, interferon-α; WT, wild type; CHR, complete hematologic response; PHR, partial hematologic response; HU, hydroxyurea; MCR, major cytogenetic response; mCR, minor cytogenetic response; 6-TG, 6-thioguanine; CCR, complete cytogenetic response; IDA, idarubicin; ARA-C, cytarabine; NA, not applicable; ND, not done; BC, blast crisis; NR, no response; TRM, transplant-related mortality; MEL, melphalan.