Clinical information on patients and results of mutation analyses before and after TKI therapies
| Patient no. . | Sex . | Before TKI therapy . | After TKI therapy . | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age (y) . | Previous therapy . | Karyotype . | BCR-ABL isoform . | FISH (B-A: %) . | qRT-PCR (B-A: ×10−6 copies per copy 18S rRNA)* . | No. of mutations . | TKI . | Duration of TKI (mo) . | Karyotype . | FISH (B-A: %) . | qRT-PCR (B-A: ×10−6 copies per copy 18S rRNA)* . | No. of mutations . | ||
| 1 | M | 32 | None | 46, XY, add(9)(q34), add(17)(q11.2), der(22)t(9;22)(q34;q11.2) [20] | b2a2 | 98.0 | n.d. | 10 | Ima | 26 | 46, XY [20] | 0 | 0.01 | 1 |
| 2 | F | 58 | IFN | 46, XX, t(9;22)(q34;q11.2) [5] / 46, XX [15] | b2a2 | n.d. | n.d. | 4 | Ima | 97 | 46, XX [20] | 0 | n.d. | 1 |
| 3 | F | 49 | None | 46, XX, t(9;22)(q34;q11.2) [20] | b3a2 | n.d. | 35.8 | 10 | Ima, Dasa | 69 | 48, XX,+5,+5 [1]/46, XX [19] | 0 | <0.01 | 0 |
| 4 | F | 49 | None | 46, XX, t(9;22)(q34;q11.2) [17]/46,XX [3] | b3a2 | n.d. | n.d. | 3 | Nilo | 18 | 46, XX [20] | 0 | n.d. | 0 |
| 5 | F | 58 | HU, IFN | 46, XX, t(9;22)(q34;q11.2) [6]/46,XX [14] | b3a2 | 25.8 | n.d. | 9 | Ima | 75 | 46, XX [20] | 0 | <0.01 | 1 |
| 6 | M | 88 | None | 46, XY, t(9;22)(q34;q11.2) [20] | b3a2 | 92.0 | n.d. | 13 | Nilo | 12 | 45, X, -Y [6]/46, XY [14] | n.d. | n.d.† | 3 |
| 7 | M | 57 | None | 46, XY, t(9;22)(q34;q11.2) [20] | b2a2 | 95.0 | 41.0 | 14 | Ima | 21 | 46, XY [20] | n.d. | <0.01 | 0 |
| 8 | F | 33 | None | 46, XX, t(9;22;15)(q34;q11.2;q26) [18] / 46, XX [2] | b2a2 | 98.0 | 17.3 | 7 | Nilo | 6 | 46, XX [20] | 0 | <0.01 | 0 |
| 9 | M | 30 | None | 46, XY, t(9;22)(q34;q11,2) [20] | b3a2 | 97.0 | 64.2 | 3 | Ima | 24 | 46, XY [20] | 0 | <0.01 | 0 |
| 10 | M | 39 | None | 46, XY, t(9;22)(q34;q11,2) [20] | b3a2 | 99.0 | 36.7 | 3 | Ima | 32 | 46, XY [20] | 0 | <0.01 | 0 |
| 11 | F | 62 | None | 46, XX, t(9;22)(q34;q11,2) [20] | b2a2 | 99.0 | 14.0 | 17 | Ima | 23 | 46, XX [20] | 0 | 0.01 | 0 |
| 12 | M | 40 | None | 46, XY, t(9;22)(q34;q11,2)[19] / 46, idem, add(3)(q26) [1] | b2a2 | 99.0 | 15.6 | 4 | Dasa | 12 | 46, XY [3] | 0 | 0.02 | 0 |
| 13 | M | 35 | HU, IFN | 46, XY, t(9;22)(q34;q11,2) [20] | b3a2 | 91.9 | n.d. | 2 | Ima | 69 | 46, XY [20] | 0 | <0.01 | 0 |
| 14 | M | 55 | MCNU, IFN | 46, XY, t(9;22)(q34;q11,2) [13]/46,XY [7] | b3a2 | 82.0 | n.d. | 4 | Ima, Nilo | 43 | 46, XY [20] | 0 | <0.01 | 7 |
| 15 | F | 60 | None | 46, XX, der(9)inv(9)(p12q13)t(9;22)(q34;q11.2), der(22)t(9;22) [20] | b3a2 | n.d. | 81.3 | 9 | Ima | 17 | 46, XX, inv(9)(p12q13) [20] | 0 | <0.01 | 0 |
| 16 | M | 54 | None | 46, XY, t(9;22)(q34;q11,2) [19]/46, XY [1] | b2a2 | 96.0 | 12.9 | 11 | Ima, Nilo | 26 | 46, XY [20] | n.d. | <0.01 | 0 |
| 17 | M | 24 | None | 46, XY, t(1;8)(q42;p23), t(9;22)(q34;q11.2) [20] | b2a2 | n.d. | 59.9 | 1 | Ima | 48 | 46. XY [20] | 0 | <0.01 | 1 |
| 18 | F | 67 | None | 46, XX, t(9;22)(q34;q11,2) [20] | b3a2 | n.d. | 16.0 | 13 | Nilo | 21 | 46, XX [20] | 0 | <0.01 | 0 |
| 19 | M | 67 | HU | 46, XY, t(9;22)(q34;q11,2) [20] | b3a2 | 96.0 | 28.1 | 8 | Ima | 110 | 46, XY [20] | 0 | 0.01 | 0 |
| 20 | M | 54 | None | 46, XY, t(9;22)(q34;q11,2) [20] | b3a2 | n.d. | 81.2 | 11 | Ima, Nilo | 30 | 46, XY [20] | 0 | <0.01 | 0 |
| Patient no. . | Sex . | Before TKI therapy . | After TKI therapy . | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age (y) . | Previous therapy . | Karyotype . | BCR-ABL isoform . | FISH (B-A: %) . | qRT-PCR (B-A: ×10−6 copies per copy 18S rRNA)* . | No. of mutations . | TKI . | Duration of TKI (mo) . | Karyotype . | FISH (B-A: %) . | qRT-PCR (B-A: ×10−6 copies per copy 18S rRNA)* . | No. of mutations . | ||
| 1 | M | 32 | None | 46, XY, add(9)(q34), add(17)(q11.2), der(22)t(9;22)(q34;q11.2) [20] | b2a2 | 98.0 | n.d. | 10 | Ima | 26 | 46, XY [20] | 0 | 0.01 | 1 |
| 2 | F | 58 | IFN | 46, XX, t(9;22)(q34;q11.2) [5] / 46, XX [15] | b2a2 | n.d. | n.d. | 4 | Ima | 97 | 46, XX [20] | 0 | n.d. | 1 |
| 3 | F | 49 | None | 46, XX, t(9;22)(q34;q11.2) [20] | b3a2 | n.d. | 35.8 | 10 | Ima, Dasa | 69 | 48, XX,+5,+5 [1]/46, XX [19] | 0 | <0.01 | 0 |
| 4 | F | 49 | None | 46, XX, t(9;22)(q34;q11.2) [17]/46,XX [3] | b3a2 | n.d. | n.d. | 3 | Nilo | 18 | 46, XX [20] | 0 | n.d. | 0 |
| 5 | F | 58 | HU, IFN | 46, XX, t(9;22)(q34;q11.2) [6]/46,XX [14] | b3a2 | 25.8 | n.d. | 9 | Ima | 75 | 46, XX [20] | 0 | <0.01 | 1 |
| 6 | M | 88 | None | 46, XY, t(9;22)(q34;q11.2) [20] | b3a2 | 92.0 | n.d. | 13 | Nilo | 12 | 45, X, -Y [6]/46, XY [14] | n.d. | n.d.† | 3 |
| 7 | M | 57 | None | 46, XY, t(9;22)(q34;q11.2) [20] | b2a2 | 95.0 | 41.0 | 14 | Ima | 21 | 46, XY [20] | n.d. | <0.01 | 0 |
| 8 | F | 33 | None | 46, XX, t(9;22;15)(q34;q11.2;q26) [18] / 46, XX [2] | b2a2 | 98.0 | 17.3 | 7 | Nilo | 6 | 46, XX [20] | 0 | <0.01 | 0 |
| 9 | M | 30 | None | 46, XY, t(9;22)(q34;q11,2) [20] | b3a2 | 97.0 | 64.2 | 3 | Ima | 24 | 46, XY [20] | 0 | <0.01 | 0 |
| 10 | M | 39 | None | 46, XY, t(9;22)(q34;q11,2) [20] | b3a2 | 99.0 | 36.7 | 3 | Ima | 32 | 46, XY [20] | 0 | <0.01 | 0 |
| 11 | F | 62 | None | 46, XX, t(9;22)(q34;q11,2) [20] | b2a2 | 99.0 | 14.0 | 17 | Ima | 23 | 46, XX [20] | 0 | 0.01 | 0 |
| 12 | M | 40 | None | 46, XY, t(9;22)(q34;q11,2)[19] / 46, idem, add(3)(q26) [1] | b2a2 | 99.0 | 15.6 | 4 | Dasa | 12 | 46, XY [3] | 0 | 0.02 | 0 |
| 13 | M | 35 | HU, IFN | 46, XY, t(9;22)(q34;q11,2) [20] | b3a2 | 91.9 | n.d. | 2 | Ima | 69 | 46, XY [20] | 0 | <0.01 | 0 |
| 14 | M | 55 | MCNU, IFN | 46, XY, t(9;22)(q34;q11,2) [13]/46,XY [7] | b3a2 | 82.0 | n.d. | 4 | Ima, Nilo | 43 | 46, XY [20] | 0 | <0.01 | 7 |
| 15 | F | 60 | None | 46, XX, der(9)inv(9)(p12q13)t(9;22)(q34;q11.2), der(22)t(9;22) [20] | b3a2 | n.d. | 81.3 | 9 | Ima | 17 | 46, XX, inv(9)(p12q13) [20] | 0 | <0.01 | 0 |
| 16 | M | 54 | None | 46, XY, t(9;22)(q34;q11,2) [19]/46, XY [1] | b2a2 | 96.0 | 12.9 | 11 | Ima, Nilo | 26 | 46, XY [20] | n.d. | <0.01 | 0 |
| 17 | M | 24 | None | 46, XY, t(1;8)(q42;p23), t(9;22)(q34;q11.2) [20] | b2a2 | n.d. | 59.9 | 1 | Ima | 48 | 46. XY [20] | 0 | <0.01 | 1 |
| 18 | F | 67 | None | 46, XX, t(9;22)(q34;q11,2) [20] | b3a2 | n.d. | 16.0 | 13 | Nilo | 21 | 46, XX [20] | 0 | <0.01 | 0 |
| 19 | M | 67 | HU | 46, XY, t(9;22)(q34;q11,2) [20] | b3a2 | 96.0 | 28.1 | 8 | Ima | 110 | 46, XY [20] | 0 | 0.01 | 0 |
| 20 | M | 54 | None | 46, XY, t(9;22)(q34;q11,2) [20] | b3a2 | n.d. | 81.2 | 11 | Ima, Nilo | 30 | 46, XY [20] | 0 | <0.01 | 0 |
B-A, BCR-ABL; Dasa, dasatinib; FISH, fluorescence in situ hybridization; HU, hydroxyurea; IFN, interferon; in/del, insertion/deletion; Ima, imatinib; MCNU, methyl chloroethyl nitroso urea; n.d., not determined; Nilo, nilotinib; qRT-PCR, quantitative reverse transcription polymerase chain reaction; rRNA, ribosomal RNA.
qRT-PCR: levels of BCR-ABL messenger RNA (mRNA) in the BM quantified using real-time RT-PCR were indicated as ×10−6 copies per copy 18S rRNA.
Minimal residual BCR-ABL mRNA in the peripheral blood for patient no. 6 was below detection limit (<5 copies per 0.5 μg RNA) using transcription-mediated amplification followed by hybridization protection assay (Amp-CML).