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Table 1 TKI-resistance of BCR-ABL1-positive cell lines

From: BCR-ABL1-independent PI3Kinase activation causing imatinib-resistance

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.
  1. IC50 values for TKI imatinib, nilotinib and dasatinib were determined by [3H]-thymidine uptake 24 h after onset of incubation with varying concentrations of the individual inhibitors (bold: TKI-resistant cell lines). Note that imatinib-resistant cell lines were also resistant to second-generation inhibitors nilotinib and dasatinib. The BCR-ABL1 kinase domain of TKI-resistant cell lines was sequenced and found to be wild-type (wt). Expression of Ikaros splice variant 6 (Ik6) was determined by conventional PCR. BCR-ABL1 mRNA expression levels in cell lines with different breakpoints (b2-a2; e1-a2) were determined with quantitative real-time PCR. BCR-ABL1 expression of cell line JK-1 was set to 1 for b2-a2 positive cell lines; for e1-a2 positive cell lines, TOM-1 was the reference cell line. B-cell BC: B blast crisis; B lymph: B lymphoblastoid; T BC: T-cell blast crisis; M BC: myeloid blast crisis; mu: mutant; wt: wild-type; n.d.: not done.