We read with great interest the article by Yagi et al1 on the expression of nonfunctional Ikaros isoform 6 (Ik6) in childhood acute myeloid leukemia (AML). The authors reported that Ik6 was expressed in 7 of 10 cases of M4 and M5 AML (French-American-British [FAB] classification), but in none with M2 and M7 AML. Their M4 and M5 cases with Ik6 expression had karyotype abnormalities: inv(16), inv(6), inv(9), del(11), +6, +8, +18, +21, or t(9;11). We also determined whether Ik6 was expressed in samples from 24 Japanese adults with AML using reverse transcriptase–polymerase chain reaction2; 7 cases of M1, 5 of M2, 2 of M3, 5 with cessation of M4, and 5 with cessation of M5. As shown in Table1, all AML samples expressed Ik1 and/or Ik2 but not Ik6. Abnormal karyotypes inv(16) (cases 17 and 18) and +8 (case 15) were also found in adult AML M4 cases; however, expression of Ik6 was not detected in these cases of AML. These findings indicate that Ik6 is expressed in childhood AML but not in adult AML, and that expression of Ik6 in AML is apparently not associated with karyotypes. Several reports demonstrated that Ik6 is frequently expressed in B-precursor acute lymphoblastic leukemia (pre-B ALL) in infants, young children,3-6 and adults, and in childhood pre-T ALL.7 We reported that Ik6 was detected in 16 of 36 patients with adult pre-B ALL but not in adult pre-T ALL.2 

Table 1.

Expression of Ikaros isoforms in adult AML

Case Age, y FAB Karyotype Ikaros isoforms 
71 M1 46,XY,del(7)(q?) Ik1, Ik2  
42 M1 46,XY Ik1 
61 M1 46,XY Ik1, Ik2 
17 M1 46,XY,−13,−17,5q+,8q+ Ik1, Ik2 
55 M1 46,XY Ik1, Ik2 
62 M1 46,XY,t(2;11)(q21;p15) Ik1, Ik2 
55 M1 45,XY,−7 Ik2 
59 M2 46,XY,t(8;21)(q23;q23) Ik1, Ik2 
65 M2 46,XY,t(8;21)(q23;q23) Ik1, Ik2 
10 38 M2 46,XY Ik1, Ik2 
11 42 M2 44,XY,−13,−14,t(5;6),t(6;11), del(14),t(14;?) Ik1, Ik2  
12 43 M2 46,XX Ik1, Ik2 
13 69 M3 46,XY,t(15;17) Ik1, Ik2 
14 51 M3 46,XX,t(15;17) Ik1, Ik2 
15 28 M4 50,XY,+8,+11,+13,+19 Ik1, Ik2 
16 58 M4 46,XY Ik1, Ik2 
17 31 M4 46,XY,inv(16)(p13;q22) Ik1, Ik2 
18 54 M4 46,XY,inv(16)(p13;q22) Ik1, Ik2 
19 56 M4 46,XX Ik1, Ik2 
20 79 M5 NT Ik1, Ik2 
21 79 M5 46,XY Ik1, Ik2 
22 25 M5 46,XX Ik1, Ik2 
23 40 M5 46,XX Ik1, Ik2 
24 86 M5 46,XX Ik1, Ik2 
Case Age, y FAB Karyotype Ikaros isoforms 
71 M1 46,XY,del(7)(q?) Ik1, Ik2  
42 M1 46,XY Ik1 
61 M1 46,XY Ik1, Ik2 
17 M1 46,XY,−13,−17,5q+,8q+ Ik1, Ik2 
55 M1 46,XY Ik1, Ik2 
62 M1 46,XY,t(2;11)(q21;p15) Ik1, Ik2 
55 M1 45,XY,−7 Ik2 
59 M2 46,XY,t(8;21)(q23;q23) Ik1, Ik2 
65 M2 46,XY,t(8;21)(q23;q23) Ik1, Ik2 
10 38 M2 46,XY Ik1, Ik2 
11 42 M2 44,XY,−13,−14,t(5;6),t(6;11), del(14),t(14;?) Ik1, Ik2  
12 43 M2 46,XX Ik1, Ik2 
13 69 M3 46,XY,t(15;17) Ik1, Ik2 
14 51 M3 46,XX,t(15;17) Ik1, Ik2 
15 28 M4 50,XY,+8,+11,+13,+19 Ik1, Ik2 
16 58 M4 46,XY Ik1, Ik2 
17 31 M4 46,XY,inv(16)(p13;q22) Ik1, Ik2 
18 54 M4 46,XY,inv(16)(p13;q22) Ik1, Ik2 
19 56 M4 46,XX Ik1, Ik2 
20 79 M5 NT Ik1, Ik2 
21 79 M5 46,XY Ik1, Ik2 
22 25 M5 46,XX Ik1, Ik2 
23 40 M5 46,XX Ik1, Ik2 
24 86 M5 46,XX Ik1, Ik2 

NT indicates not tested.

Although the role of nonfunctional Ikaros isoforms in leukemogenic mechanisms is not fully understood, it should be kept in mind that the expression manner of IK-6 differs in adult, childhood, and infant acute leukemias.

Supported by research grants from the Ministry of Education, Culture, Sports, Science, and Technology from the Ministry of Health, Labour, and Welfare, Tokyo, Japan.

References

References
1
Yagi
T
Hibi
S
Takanashi
M
et al. 
High frequency of Ikaros isoform 6 expression in acute myelomonocytic and monocytic leukemias: implications for up-regulation of the antiapoptotic protein Bcl-XL in leukemogenesis.
Blood.
99
2002
1350
1355
2
Nishii
K
Katayama
N
Miwa
H
et al. 
Non-DNA-binding Ikaros isoform gene expressed in adult B-precursor acute lymphoblastic leukemia.
Leukemia.
16
2002
1285
1292
3
Sun
L
Heerema
N
Crotty
L
et al. 
Expression of dominant-negative and mutant isoforms of the antileukemic transcription factor Ikaros in infant acute lymphoblastic leukemia.
Proc Natl Acad Sci USA.
96
1999
680
685
4
Sun
L
Goodman
PA
Wood
CM
et al. 
Expression of aberrantly spliced oncogenic Ikaros isoforms in childhood acute lymphoblastic leukemia.
J Clin Oncol.
17
1999
3753
3766
5
Nakase
K
Ishimaru
F
Avitahl
N
et al. 
Dominant negative isoform of the Ikaros gene in patients with adult B-cell acute lymphoblastic leukemia.
Cancer Res.
60
2000
4062
4065
6
Olivero
S
Maroc
C
Beillard
E
et al. 
Detection of different Ikaros isoforms in human leukaemias using real-time quantitative polymerase chain reaction.
Br J Haematol
110
2000
826
830
7
Sun
L
Crotty
M-L
Sensel
M
et al. 
Expression of dominant-negative Ikaros isoforms in T-cell acute lymphoblastic leukemia.
Clin Cancer Res.
7
1999
2112
2120