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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.