Fumihiko Hayakawa

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Arsenic trioxide (As₂O₃) is a highly effective treatment for patients with refractory/relapsed acute promyelocytic leukemia (APL), but resistance to As₂O₃ has recently been seen. In the present study, we report the findings that 2 of 15 patients with refractory/relapsed APL treated with As₂O₃ were clinically As₂O₃ resistant. Leukemia cells from these 2(More)
We have recently identified an internal tandem duplication of the human Flt3 gene in approximately 20% of acute myeloid leukemia (AML) cases. In the present study, the wild-type and the mutant Flt3 genes were transfected into two IL-3-dependent cell lines, 32D and BA/F3 cells. Mutant Flt3-transfected cells exhibited autonomous growth while wild-type(More)
OBJECTIVE We investigated the mechanism responsible for imatinib (IM) resistance in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) cell lines. METHODS We established cell lines from a patient with Ph(+) ALL at the time of first diagnosis and relapsed phase and designated as NPhA1 and NPhA2, respectively. We also derived(More)
Fms-like tyrosine kinase 3 (FLT3) is expressed in hematopoietic progenitor cells. An internal tandem duplication (ITD) of FLT3 (FLT3/ITD) is the most frequent mutation in human adult acute myeloid leukemia (AML). FLT3/ITD contributes to the constitutive activation of FLT3 itself and its downstream signal components, mitogen-activated protein kinase and(More)
The promyelocytic leukemia (PML) protein is a potent growth suppressor and proapototic factor, whereas aberrant fusions of PML and retinoic acid receptor (RAR)-alpha are causal agents in human acute promyelocytic leukemia. Arsenic trioxide (As(2)O(3)) treatment induces apoptosis in acute promyelocytic leukemia cells through an incompletely understood(More)
Signal transduction and activator of transcription (STAT) proteins are extracellular ligand-responsive transcription factors that mediate cell proliferation, apoptosis, differentiation, development and the immune response. Aberrant signals of STAT induce uncontrolled cell proliferation and apoptosis resistance and are strongly involved in cancer. STAT has(More)
The zinc finger transcription factor GATA-2 plays a critical role in the survival and proliferation of hematopoietic stem cells. This study examined the interaction of GATA-2 with histone deacetylases (HDACs) to define the involvement of HDACs in the regulation of GATA-2 function. GATA-2 directly associates with HDAC3 but not with HDAC1. Consistent with(More)
Transcription factor c-Myb plays important roles in cell survival and differentiation in immature hematopoietic cells. Here we demonstrate that c-Myb is acetylated at the carboxyl-terminal conserved domain by histone acetyltransferase p300 both in vitro and in vivo. The acetylation sites in vivo have been located at the lysine residues of the conserved(More)
Many cytokines and growth factors stimulate multiple signal transduction pathways essential for proliferation in human acute leukaemia cells, including a mitogen-activated protein (MAP) kinase pathway and a Janus kinase (JAK)-STAT (signal transducers and activators of transcription) pathway. We have previously shown constitutive activation of MAP kinase in(More)
The DNA cleavage activities of (+)-catechin (C), (-)-epicatechin (EC), (-)-epigallocatechin (EGC), and (-)-epigallocatechin gallate (EGCg) were examined with 16 different metal ions. Cu(2+) with all the catechins facilitated DNA cleavage, while Ag+ with EGC and EC showed a strong repressive effect. The other metal ions examined showed little effect.