Background
Results and Discussion
Imatinib-resistant BCR-ABL1 positive cell lines
CML | stage | IC50 imatinib (nM) | IC50 nilotinib (nM) | IC50 dasatinib (nM) | BCR-ABL1 mu/wt | BCR-ABL1 breakpoint | Ikaros Ik6 | BCR-ABL1 mRNA expression level |
---|---|---|---|---|---|---|---|---|
BV-173 | B BC | 100 | < 10 | n.d. | n.d. | b2-a2 | yes | 1.6 |
CML-T1 | T BC | 200 | 20 | n.d. | n.d. | b2-a2 | no | 0.5 |
EM-2 | M BC | 80 | < 10 | n.d. | wt | b3-a2 | no | n.d. |
HNT-34 | M BC | 100 | 10 | n.d. | n.d. | b3-a2 | no | n.d. |
JK-1 | M BC | 100 | 10 | n.d. | n.d. | b2-a2 | no | 1 |
JURL-MK1 | M BC | 200 | < 10 | < 1 | n.d. | b3-a2 | no | n.d. |
JURL-MK2 | M BC | 50 | < 10 | < 1 | n.d. | b3-a2 | no | n.d. |
K-562 | M BC | 200 | 20 | n.d. | n.d. | b3-a2 | no | n.d. |
KCL-22
| M BC | 800 | 40 | 1 | wt | b2-a2 | no | 1.7 |
KU-812 | M BC | 50 | < 10 | n.d. | n.d. | b3-a2 | no | n.d. |
KYO-1 | M BC | 80 | < 10 | < 1 | n.d. | b2-a2 | no | 0.9 |
LAMA-84 | M BC | 100 | < 10 | < 1 | n.d. | b3-a2 | no | n.d. |
MEG-01 | M BC | 200 | < 10 | < 1 | n.d. | b2-a2 | no | n.d. |
MOLM-6 | M BC | 50 | < 10 | < 1 | n.d. | b2-a2 | no | n.d. |
NALM-1
| B BC | > 10000 | 5000 | > 1000 | wt | b2-a2 | no | 1 |
pre B-ALL
| ||||||||
SD-1
| B lymph | > 10000 | 2000 | n.d. | wt | e1-a2 | no | 0.1 |
SUP-B15
| pre B | 2000 | 500 | 100 | wt | e1-a2 | yes | 1.1 |
TOM-1 | pre B | 80 | 5 | n.d. | n.d. | e1-a2 | no | 1 |
T-ALL
| ||||||||
MHH-TALL-1
| T-ALL | 1000 | 1000 | n.d. | wt | e6-a2 | no | n.d. |
BCR-ABL1 mutations, BCR-ABL1 expression, imatinib transporters
SRC kinases
Imatinib induces dephosphorylation of ERK1/2 and of STAT5 in TKI-resistant cell lines
BCR-ABL1-resistant cell lines show constitutive activation of mTORC1
[3H]-thymidine (SI) | % cells in G1 | |||
---|---|---|---|---|
control | rapamycin | control | rapamycin | |
TKI-sensitive
| ||||
BV-173 | 1 | 0.3 +/- 0.1 | 63 +/- 4 | 69 +/- 4 |
EM-2 | 1 | 0.5 +/- 0.1 | 61 +/- 2 | 68 +/- 1 |
JURL-MK2 | 1 | 0.6 +/- 0.1 | 73 +/- 1 | 81 +/- 2 |
TKI-resistant
| ||||
KCL-22 | 1 | 0.4 +/- 0 | 60 +/- 5 | 74 +/- 2 |
NALM-1 | 1 | 0.6 +/- 0.1 | 76 +/- 2 | 80 +/- 1 |
SUP-B15 | 1 | 0.5 +/- 0.1 | 66 +/- 1 | 83 +/- 2 |