Establishment of a human acute myeloid leukemia cell line (Kasumi-1) with 8;21 chromosome translocation

Asou, Hiroya; Tashiro, S; Hamamoto, Kazuko; Otsuji, Akira; Kita, Kouhei; Kamada, Nanao

doi:10.1182/blood.v77.9.2031.bloodjournal7792031

Cited by 43 publications

(43 citation statements)

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“…21 Kasumi-1, a cell line of AML (FAB classification M2) with 8;21 chromosome translocation (t(8;21)), was a kind gift from Dr. H. Asou (Hiroshima University, Hiroshima, Japan). 22…”

Section: Cell Culture and Characterizationmentioning

confidence: 99%

CD82 regulates STAT5/IL‐10 and supports survival of acute myelogenous leukemia cells

Nishioka

Ikezoe

Yang

et al. 2013

Intl Journal of Cancer

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We recently reported that adhesion molecule CD82 is aberrantly expressed in CD34 1 =CD38 2 leukemia stem cells (LSCs). Here, we report the results of a functional analysis of CD82 in CD34 1 =CD38 2 acute myelogenous leukemia (AML) cells. Short hairpin (sh)RNA-mediated downregulation of CD82 resulted in a decrease in the level of IL-10. In contrast, forced expression of CD82 in CD34 1 =CD38 1 AML cells by transduction with CD82-expressing lentiviral particles resulted in an increase in the levels of IL-10. Notably, exposure of CD34 1 =CD38 2 AML cells to IL-10 stimulated clonogenic growth of these cells. Moreover, downregulation of CD82 by a shRNA dephosphorylated STAT5 in CD34 1 =CD38 2 AML cells. On the other hand, forced expression of CD82 resulted in increase in the levels of p-STAT5 in CD34 1 =CD38 1 AML cells. Chromatin immunoprecipitation (ChIP) assay results indicated that STAT5A binds to the promoter region of the IL-10 gene, while reporter gene assay results indicated stimulation of IL-10 expression at the transcriptional level. These results suggest that CD82 positively regulates the STAT5=IL-10 signaling pathway. Moreover, shRNA-mediated downregulation of CD82 expression in CD34 1 =CD38 -AML cells dephosphorylated STAT5 in immunodeficient mice. Taken together, our data suggest that the CD82=STAT5=IL-10 signaling pathway is involved in the survival of CD34 1 =CD38 2 AML cells and may thus be a promising therapeutic target for eradication of AML LSCs.Acute myelogenous leukemia (AML) is initiated and maintained by a subset of self-renewing leukemia stem cells (LSCs). 1 Novel treatment strategies targeting LSCs are thus urgently needed if a cure for AML is to be developed. Studies in which AML has been generated in immunocompromised mice have shown that LSCs have the self-renewal potency and generate AML in severely immunocompromised mice. 2,3 In addition, CD34 1 =CD38 2 AML cells fulfill the criteria for LSCs in vivo. 2,3 However, recent studies involving more severely immunocompromised mice found that in some cases, even CD34 2 or CD38 1 AMLs cells can be used to reconstitute AML. 4,5 Cytokine=receptor signaling is important to the survival of hematopoietic stem cells (HSCs) and their occupancy within the bone marrow (BM) niche. For example, signaling via the stem cell factor (SCF) thrombopoietin (TPO)/c-Mpl and chemokine stromal cell-derived factor-1 (SDF-1)/CXC receptor 4 (CXCR4) regulate HSC quiescence and engraftment of HSCs into the BM niche, 6-9 although many details of the molecular mechanisms through which these signal pathways regulate hematopoiesis remain to be elucidated.Deletion of signal transducer and activator of transcription 5 (STAT5) stimulates cell cycling in HSCs in association with downregulation of Tie and p53, 10 which play an important role in engraftment of these cells into the BM niche via modulation of c-Mpl signaling. 11,12 Moreover, long-term repopulating activity is impaired in STAT5-deficient CD34 1 AML cells and HSCs. 13,14 These observations suggest that STAT5 is require...

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“…21 Kasumi-1, a cell line of AML (FAB classification M2) with 8;21 chromosome translocation (t(8;21)), was a kind gift from Dr. H. Asou (Hiroshima University, Hiroshima, Japan). 22…”

Section: Cell Culture and Characterizationmentioning

confidence: 99%

CD82 regulates STAT5/IL‐10 and supports survival of acute myelogenous leukemia cells

Nishioka

Ikezoe

Yang

et al. 2013

Intl Journal of Cancer

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“…Karyotype analysis. A karyotype analysis was performed on aspirated BM cells, as described previously (Asou et al, 1991).…”

Section: Methodsmentioning

confidence: 99%

Myeloid differentiation antigen and cytokine receptor expression on acute myelocytic leukaemia cells with t(16;21)(p11;q22): frequent expression of CD56 and interleukin‐2 receptor α chain

et al. 1999

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Summary.We report the cellular characteristics of cells from three patients with de novo acute myelocytic leukaemia (AML) with t(16;21)(p11;q22), two M4 and one M5a according to the FAB classification, and two permanent cell lines with t(16;21)(p11;q22), TSU1621MT and YNH-1. The FUS/ERG fusion mRNA was demonstrated in all cases by reverse transcriptase-polymerase chain reaction (RT-PCR). The immunophenotypes of the AML cells, and YNH-1 and TSU1621MT cell lines with t(16;21) were characterized as CD34Cells from all samples strongly expressed c-kit, granulocyte colony-stimulating factor receptor (G-CSFR), c-fms (macrophage colony-stimulating factor receptor), interleukin-3 receptor a chain (IL-3Ra), and granulocyte macrophage colony-stimulating factor receptor a chain (GM-CSFRa), and these data corresponded well to the growth responsiveness to the cytokines. IL-2Ra expression was also found in all t(16;21) samples, but IL-2 did not act on the proliferation of the leukaemic cells in in vitro cultures. G-CSF distinctly promoted the proliferation of leukaemic cells of t(16;21) AML, but did not enhance the expression of MPO and neutrophil differentiation of these cells. Our findings indicate that AML cells with t(16;21) preserve stem cell properties such as CD34 and c-kit expression, and suggest that they have the potential to differentiate into a monocytic lineage. The relationship between the unique cellular characteristics (especially CD56 and IL-2Ra expression) and FUS/ERG protein remains undetermined.

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“…The Kasumi-1 and SKNO-1 cell lines (Asou et al, 1991;Matozaki et al, 1995) were obtained courtesy of Dr M. Lübbert (University of Freiburg). The cells were maintained in RPMI-1640 medium supplemented with 10% fetal bovine serum, penicillin/streptomycin and l-glutamine.…”

Section: Cell Lines and Cell Culturementioning

confidence: 99%

AKAP12, a gene with tumour suppressor properties, is a target of promoter DNA methylation in childhood myeloid malignancies

et al. 2007

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Summary A‐kinase anchor protein 12 (AKAP12) is a scaffold protein that participates in mitotic regulation and other signalling processes and probably exerts tumour suppressor function. We hypothesized that epigenetic repression of the AKAP12 gene might occur in malignant myeloid disorders. This study demonstrated that the 5′ CpG island of AKAP12 was unmethylated in normal haematopoietic progenitors and granulocytes but exhibited profound methylation in Kasumi‐1 and SKNO‐1 leukaemic myeloblasts. Correspondingly, AKAP12 was expressed in normal progenitors but transcriptionally silent in leukaemic blasts. Re‐expression of AKAP12 in Kasumi‐1 and SKNO‐1 cells was accomplished by treatment with MS275 alone or in combination with zebularine, indicating epigenetic mechanisms of gene repression. AKAP12 hypermethylation was found in one case of refractory anaemia with excess blasts (RAEB) and two cases of acute myeloid leukaemia (AML) in a panel of 21 blood or bone marrow samples from children with malignant myeloid disorders including refractory cytopenia, RAEB, juvenile myelomonocytic leukaemia and AML. While AKAP12 function has not been previously linked to leukaemogenesis, our results raise the possibility that epigenetic silencing of AKAP12 is involved in myeloid malignancies.

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Establishment of a human acute myeloid leukemia cell line (Kasumi-1) with 8;21 chromosome translocation

Cited by 43 publications

References 0 publications

CD82 regulates STAT5/IL‐10 and supports survival of acute myelogenous leukemia cells

CD82 regulates STAT5/IL‐10 and supports survival of acute myelogenous leukemia cells

Myeloid differentiation antigen and cytokine receptor expression on acute myelocytic leukaemia cells with t(16;21)(p11;q22): frequent expression of CD56 and interleukin‐2 receptor α chain

AKAP12, a gene with tumour suppressor properties, is a target of promoter DNA methylation in childhood myeloid malignancies

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