|Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
Ikaros, a zinc finger transcription factor, is essential for lymphoid development. We examined the expression of Ikaros isoforms in 11 leukemic cell lines and adult acute lymphoblastic leukemia cells from 36 patients with B-precursor acute lymphoblastic leukemia (pre-B ALL) and nine with T-precursor acute lymphoblastic leukemia (pre-T ALL), using RT-PCR analysis. In one pre-B ALL cell line, INC cells, and primary leukemic cells from 16 patients with pre-B ALL, we found the predominant expression of a non-DNA-binding Ikaros isoform, Ik-6. However, Ik-6 was not detected in pre-T ALL cells. All of pre-B ALL cells expressing Ik-6 were CD10^+, whereas CD10^- pre-B ALL cells did not express Ik-6. The expression of Ik-6 was not related to karyotype abnormalities such as t(9 ; 22) and t(4 ; 11). Proteins from the cells that expressed Ik-6 alone failed to bind to the Ikaros protein-specific binding sequence in DNA. Ikaros proteins lacking the DNA binding sequences were detected in the cytoplasm
but not in the nucleus of the cells. When INC and primary pre-B ALL cells that express Ik-6 alone were irradiated and cultured in the absence of serum, these cells produced functional Ikaros isoforms, lk-1 and Ik-2. Purified CD19^+ CD10^- and CD19^+ CD10^+ cells from normal human bone marrow did not express Ik-6. The predominant expression of Ik-6, which is the result of post-transcription dysregulation, is characteristic of adult pre-B ALL, especially CD10^+ pre-B ALL. We also determined if Ik6 was expressed in samples from 24 Japanese adults with AML, using RT-PCR ; 7 cases of M1, 5 of M2, 2 of M3, 5 with cessation of M4, and 5 with of M5. All AML samples expressed Ik1 and/or Ik2 but not Ik6. These findings indicate that Ik-6 is expressed in childhood AML but not in adult AML. Several reports demonstrated that Ik6 is frequently expressed in pre-B ALL of infants, young children, and adults, and in pre-T ALL of childhood. We reported that Ik-6 was detected in only adult pre-B ALL but not in adult pre-T ALL and AML.
Although the role of non-functional Ikaros isoforms in leukemogenic mechanisms is not fully understood, if should be kept in mine that Ik6 is expressed in a different manner among adult, childhood, and infant acute leukemias. Less