PMID- 10463586
OWN - NLM
STAT- MEDLINE
DCOM- 19990916
LR  - 20071115
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 59
IP  - 16
DP  - 1999 Aug 15
TI  - Decreases in Ikaros activity correlate with blast crisis in patients with chronic
      myelogenous leukemia.
PG  - 3931-4
AB  - Gene targeting studies in mice have shown that the lack of Ikaros activity leads 
      to T-cell hyperproliferation and T-cell neoplasia, establishing the Ikaros gene
      as a tumor suppressor gene in mice. This prompted us to investigate whether
      mutations in Ikaros play a role in human hematological malignancies. Reverse
      transcription-PCR was used to determine the relative expression levels of Ikaros 
      isoforms in a panel of human leukemia/lymphoma cell lines and human bone marrow
      samples from patients with hematological malignancies. Among the cell lines
      examined, only BV-173, which was derived from a chronic myelogenous leukemia
      (CML) patient in lymphoid blast crisis, overexpressed the dominant-negative
      isoform, Ik-6. In 9 of 17 samples of patients in blast crisis of CML, Ikaros
      activity had been reduced either by drastically reducing mRNA expression (4 of
      17) or by overexpressing the dominant-negative isoform Ik-6 (5 of 17).
      Significantly, expression of Ikaros isoforms seemed normal in chronic phase CML
      patients and patients with other hematological malignancies. In some cases,
      overexpression of the dominant-negative Ik-6 protein was confirmed by Western
      blot analysis, and Southern blot analysis indicated that decreases in Ikaros
      activity correlated with a mutation in the Ikaros locus. In summary, these
      findings suggest that a reduction of Ikaros activity may be an important step in 
      the development of blast crisis in CML and provide further evidence that
      mutations that alter Ikaros expression may contribute to human hematological
      malignancies.
FAU - Nakayama, H
AU  - Nakayama H
AD  - Department of Medicine, University of Okayama, Japan.
FAU - Ishimaru, F
AU  - Ishimaru F
FAU - Avitahl, N
AU  - Avitahl N
FAU - Sezaki, N
AU  - Sezaki N
FAU - Fujii, N
AU  - Fujii N
FAU - Nakase, K
AU  - Nakase K
FAU - Ninomiya, Y
AU  - Ninomiya Y
FAU - Harashima, A
AU  - Harashima A
FAU - Minowada, J
AU  - Minowada J
FAU - Tsuchiyama, J
AU  - Tsuchiyama J
FAU - Imajoh, K
AU  - Imajoh K
FAU - Tsubota, T
AU  - Tsubota T
FAU - Fukuda, S
AU  - Fukuda S
FAU - Sezaki, T
AU  - Sezaki T
FAU - Kojima, K
AU  - Kojima K
FAU - Hara, M
AU  - Hara M
FAU - Takimoto, H
AU  - Takimoto H
FAU - Yorimitsu, S
AU  - Yorimitsu S
FAU - Takahashi, I
AU  - Takahashi I
FAU - Miyata, A
AU  - Miyata A
FAU - Taniguchi, S
AU  - Taniguchi S
FAU - Tokunaga, Y
AU  - Tokunaga Y
FAU - Gondo, H
AU  - Gondo H
FAU - Niho, Y
AU  - Niho Y
FAU - Harada, M
AU  - Harada M
AU  - et al.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (IKZF1 protein, human)
RN  - 0 (Transcription Factors)
RN  - 0 (Zfpn1a1 protein, mouse)
RN  - 148971-36-2 (Ikaros Transcription Factor)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Blast Crisis/genetics
MH  - *DNA-Binding Proteins
MH  - Female
MH  - *Gene Expression Regulation, Neoplastic
MH  - Genes, Tumor Suppressor
MH  - Humans
MH  - Ikaros Transcription Factor
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*genetics/*pathology
MH  - Male
MH  - Mice
MH  - Middle Aged
MH  - Mutation
MH  - Transcription Factors/biosynthesis/*genetics
EDAT- 1999/08/27 00:00
MHDA- 1999/08/27 00:01
CRDT- 1999/08/27 00:00
PHST- 1999/08/27 00:00 [pubmed]
PHST- 1999/08/27 00:01 [medline]
PHST- 1999/08/27 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1999 Aug 15;59(16):3931-4.