Detection of BCR-ABL kinase domain mutations in patients with chronic myeloid leukemia on imatinib

Figures & data

Table 1. Characteristics of 110 CML patients with resistance or suboptimal response to imatinib

Parameter	Median (range) or no. (%)
Patients	n = 110
Age (years)	42(10–83)
Sex	M:67(61)
	F: 43(39)
Therapy before imatinib	25(23)
Disease phase	CP: 93(84)
	AP: 4(4)
	BP: 13(12)
Response to imatinib at time of mutation analysis according to BCR-ABL/ABL in percent	0.1–1 (CCyR): 22(20)
	1–10 (PCyR): 29(26)
	>10 (<PCyR): 59(54)
Duration of disease (months)	54(7–192)
qRT-PCR (percentage ratio of BCR-ABL/ABL)	27(0.1–258)

CP, chronic phase; AP, accelerated phase; BP, blastic phase; PCyR, partial cytogenetic response; CCyR, complete cytogenetic response.

Table 2. Patient's details with detection of kinase domain mutations

Patient number	Sex	Age (years)	Phases	Response to imatinib at time of mutation analysis	Duration of disease (months)	Nucleotide exchange in BCR-ABL	Codon exchange in BCR-ABL	Mutation	Amino acid change	BCR-ABL/ABL ratio (%)
1	M	42	CP	<PCyR	36	A1094G	ATG to GTG	M244V	Met to Val	11.7
						A1722C	GAG to GCG	E453A	Glu to Ala
2	M	45	CP	<PCyR	72	A1094G	ATG to GTG	M244V	Met to Val	14.8
3	M	29	CP	PCyR	21	A1094G	ATG to GTG	M244V	Met to Val	6.16
4	F	47	AP	<PCyR	30	G1113A	GGG to GAG	G250E	Gly to Glu	23.5
5	M	35	CP	<PCyR	12	G1113A	GGG to GAG	G250E	Gly to Glu	19.3
6	M	74	CP	<PCyR	71	G1113A	GGG to GAG	G250E	Gly to Glu	60
7	M	55	CP	<PCyR	48	G1113A	GGG to GAG	G250E	Gly to Glu	21
8	M	51	BP	<PCyR	118	G1113A	GGG to GAG	G250E	Gly to Glu	19.1
9	M	65	AP	<PCyR	60	T1121C	TAC to CAC	Y253H	Tyr to His	60
10	M	50	CP	<PCyR	70	A1128T	GAG to GTG	E255V	Glu to Val	70.2
11	M	35	CP	PCyR	32	G1127A	GAG to AAG	E255K	Glu to Lys	1.1
12	M	64	BP	<PCyR	54	G1127A	GAG to AAG	E255K	Glu to Lys	46.9
13	F	48	CP	<PCyR	118	G1190A	GAC to AAC	D276N	Asp to Asn	18.90
14	M	43	BP	<PCyR	45	A1200C	GAG to GCG	E279A	Glu to Ala	258
15	F	50	BP	<PCyR	121	C1308T	ACT to ATT	T315I	Thr to Ile	86.6
16	M	54	AP	<PCyR	29	C1308T	ACT to ATT	T315I	Thr to Ile	21.8
17	F	62	AP	<PCyR	15	C1308T	ACT to ATT	T315I	Thr to Ile	67.60
18	M	12	BP	<PCyR	36	C1308T	ACT to ATT	T315I	Thr to Ile	45
19	M	35	CP	<PCyR	50	C1315G	TTC to TTG	F317L	Phe to Leu	42
20	F	27	CP	<PCyR	118	T1416C	ATG to ACG	M351T	Met to Thr	75.5
						G1525C	TTG to TTC	L387F	Leu to Phe
21	M	41	CP	<PCyR	44	T1416C	ATG to ACG	M351T	Met to Thr	50
22	M	42	CP	<PCyR	18	A1428G	GAG to GGG	E355G	Glu to Gly	52
23	F	30	BP	<PCyR	34	T1439G	TTC to GGC	F359V	Phe to Val	55
24	M	47	CP	CCyR	45	T1439G	TTC to GTC	F359V	Phe to Val	0.1
25	F	60	CP	<PCyR	7	T1440G	TTC to TGC	F359C	Phe to Cys	69
26	F	42	CP	<PCyR	60	T1440G	TTC to TGC	F359C	Phe to Cys	45.8
27	M	60	CP	<PCyR	24	T1440G	TTC to TGC	F359C	Phe to Cys	37.40
28	M	25	CP	<PCyR	32	T1523A	TTG to ATG	L387M	Leu to Met	52.8
29	F	32	CP	CCyR	36	A1551G	CAT to CGT	H396R	His to Arg	0.28
30	M	45	CP	<PCyR	84	C1677G	TCC to TGC	S438C	Ser to Cys	27.3
31	F	49	AP	<PCyR	100	A1740G	GAG to GGG	E459G	Glu to Gly	34.2
32	F	44	CP	CCyR	36	A1740G	GAG to GGG	E459G	Glu to Gly	0.2

Nucleotide positions in coding DNA, according to GenBank accession number X16416.

CP, chronic phase; AP, accelerated phase; BP, blastic phase; PCyR, less than partial cytogenetic response; CCyR, complete cytogenetic response.

Table 3. Distribution of kinase domain mutations

Site of mutation	Mutation	Frequency
N-terminal	M244V	3
P-loop	G250E	5
	Y253H	1
	E255K	2
	E255V	1
C-helix	D276N	1
	E279A	1
ATP-binding region (drug contact sites)	T315I	4
	F317L	1
SH2-contact	M351T	2
	E355G	1
Substrate-binding region (drug contact site)	F359V	2
	F359C	3
A-loop	L387M	1
	L387F	1
	H396R	1
C-terminal	S438C	1
	E453A	1
	E459G	2