Downregulation of Wilms' tumor gene (wt1) during myelomonocytic differentiation in HL60 cells

Sekiya, Masuo; Adachi, M; Hinoda, Yuji; Imai, K; Yachi, Akira

doi:10.1182/blood.v83.7.1876.bloodjournal8371876

Cited by 17 publications

(17 citation statements)

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“…This reported that they have found mutations in the WT1 gene in 4 of 36 acute leukemia samples by SSCP analysis. The is consistent with the findings that the WT1 expression was downregulated during the differentiation of HL60 cells by mutations comprise small insertions in exons 1 and 7 and a nonsense mutation in exon 9, predicting the production of a dimethyl sulfoxide or retinoic acid 38 and during induction of erythroid and megakaryocytic differentiation of K562 cells. 39 truncated WT1 protein with absence or disruption of the zinc megakaryocyte-related transcription factor GATA-1.…”

Section: Very Low or Undetectable Levels Of Wt1 Expression Insupporting

confidence: 91%

Aberrant Overexpression of the Wilms Tumor Gene (WT1) in Human Leukemia

Inoue

Ogawa

Sonoda

et al. 1997

Blood

322

103

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To clarify whether the expression of the WT1 gene in leukemic cells is aberrant or merely reflects that in normal counterparts, the expression levels of the WT1 gene were quantitated for normal hematopoietic progenitor cells. Bone marrow (BM) and umbilical cord blood (CB) cells were fluorescence-activated cell sorting (FACS)-sorted into CD34+ and CD34− cell populations, and the CD34+ cells into nine subsets (CD34+CD33−, CD34+CD33+, CD34+CD38−, CD34+CD38+, CD34+HLA-DR−, CD34+HLA-DR+, CD34+c-kithigh, CD34+c-kitlow, and CD34+c-kit−) according to the expression levels of CD34, CD33, CD38, HLA-DR, and c-kit. Moreover, acute myeloid leukemic cells were also FACS-sorted into four populations (CD34+CD33−, CD34+CD33+, CD34− CD33+, and CD34− CD33−). FACS-sorted normal hematopoietic progenitor and leukemic cells and FACS-unsorted leukemic cells were examined for the WT1 expression by quantitative reverse transcriptase-polymerase chain reaction. The WT1 expression in the CD34+ and CD34− cell populations and in the nine CD34+ subsets of BM and CB was at either very low (1.0 to 2.4 × 10−2) or undetectable (<10−2) levels (the WT1 expression level of K562 cells was defined as 1.0), whereas the average levels of WT1 expression in FACS-sorted and -unsorted leukemic cells were 2.4 to 9.3 × 10−1. Thus, the WT1 expression levels in normal hematopoietic progenitor cells were at least 10 times less than those in leukemic cells. Therefore, we could not find any normal counterparts of BM or CB that expressed the WT1 at levels comparable with those in leukemic cells. These results indicate an aberrant overexpression of the WT1 gene in leukemic cells and imply the involvement of this gene in human leukemogenesis.

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Section: Very Low or Undetectable Levels Of Wt1 Expression Insupporting

confidence: 91%

Aberrant Overexpression of the Wilms Tumor Gene (WT1) in Human Leukemia

Inoue

Ogawa

Sonoda

et al. 1997

Blood

322

103

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“…The human leukaemic cell lines U937, K562 and HL60 were investigated. K562 and HL60 are both known to express high levels of WT1 (Sekiya et al , 1994), whereas U937 lacks detectable WT1 expression (Svedberg et al , 1998). GATA1 expression has been described in K562 (Zhang et al , 1997).…”

Section: Cell Linesmentioning

confidence: 99%

Possible regulation of Wilms’ tumour gene 1 (WT1) expression by the paired box genes PAX2 and PAX8 and by the haematopoietic transcription factor GATA‐1 in human acute myeloid leukaemias

et al. 2003

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Summary. Overexpression of the embryonic transcription factor, Wilms' tumour protein 1 (WT1), is common in acute myeloid leukaemias (AML). Mutations of Wilms' tumour gene 1 (WT1) in AML are rare and WT1 expression may be increased by other transcription factors. PAX2, PAX8 and GATA-1 are known physiological regulators of WT1. In the present study, we analysed either bone marrow or blood samples of 43 AML patients for the expression levels of WT1, PAX2, PAX8 and GATA-1 by real-time reverse transcription polymerase chain reaction (LightCycler). Bone marrow samples of patients without haematological malignancies and stem cell preparation samples from healthy donors and lymphoma patients served as controls. PAX2 expression was found in 11 of 43 AML samples, with a clear correlation of PAX2 with WT1 expression levels observed. PAX8 expression was found in two additional samples. GATA-1 expression was detectable in 41 of 43 AML samples and also in all control samples; no significant differences between these groups were observed and no correlation of GATA-1 expression with WT1 expression levels was apparent. In conclusion, PAX2, and possibly PAX8, appears to be a candidate for the upregulation of WT1 in a proportion of AML, whereas GATA-1 expression cannot be explained as an inducer of WT1. In two-thirds of leukaemias from our series, the basis of WT1 upregulation cannot be explained by the simple upregulation of the known WT1 activators.

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“…These isoforms show differences in DNA binding, affinity and their localization inside the cell (106). During hemopoiesis, WT1 is expressed mainly in CD34 + progenitor cells, and its mRNA levels decrease as the cells differentiate (107–109). The effects of WT1 on gene expression are complex, because it interacts with other transcription regulation factors.…”

Section: Gene Mutationsmentioning

confidence: 99%

GENETIC PROFILEOF ACUTE MYELOID LEUKEMIA

Mecucci

Rosati

Starza

2002

Rev Clin Exp Hematol

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Understanding genomic events and the cascade of their effects in cell function is crucial for identifying distinct subsets of acute myeloid leukemia and developing new therapeutic strategies. Conventional cytogenetics, fluorescence in situ hybridization investigations and molecular studies have provided much information over the past few years. This review will focus on major genomic mechanisms in acute myeloid luekemia and on the genes implicated in the pathogenesis of specific subtypes.

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Downregulation of Wilms' tumor gene (wt1) during myelomonocytic differentiation in HL60 cells

Cited by 17 publications

References 0 publications

Aberrant Overexpression of the Wilms Tumor Gene (WT1) in Human Leukemia

Aberrant Overexpression of the Wilms Tumor Gene (WT1) in Human Leukemia

Possible regulation of Wilms’ tumour gene 1 (WT1) expression by the paired box genes PAX2 and PAX8 and by the haematopoietic transcription factor GATA‐1 in human acute myeloid leukaemias

GENETIC PROFILEOF ACUTE MYELOID LEUKEMIA

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