BACKGROUND/AIMS It has been demonstrated that KRAS mutations represent about 90% of cancer-associated mutations, and that KRAS mutations play an essential role in neoplastic transformation. Cancer-associated RAS mutations occur frequently in acute myeloid leukemia (AML), suggesting a functional role for Ras in leukemogenesis. METHODS We successfully established a mouse model of human leukemia...

One of the most common translocations in acute myeloid leukemia (AML) is the t(8;21), which produces the fusion gene AML1-MTG8. We have developed a sensitive competitive reverse transcriptase-polymerase chain reaction (RT-PCR) assay for AML1-MTG8 transcripts, coupled with a competitive RT-PCR for the ABL transcript as a control to accurately estimate the level of amplifiable RNA. We have shown ...

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by proliferation of one or more myeloid cell lineages. Some patients exhibit leukemic transformation (LT) by unknown mechanisms, and chemotherapy may increase the risk of LT. To clarify the molecular mechanisms of LT, gene alterations involved in LT from patients in the chronic phase (CP) of MPNs were...

Angiogenesis is an important event for embryonic organogenesis as well as for tissue repair in the adult. Here, we show that hematopoietic stem cells (HSCs) play important roles for angiogenesis during embryogenesis. To investigate the role of HSCs in endothelial cell (EC) development, we analyzed AML1-deficient embryos, which lack definitive hematopoiesis. These embryos showed defective angiog...

The AML1 gene encoding the DNA-binding alpha-subunit in the Runt domain family of heterodimeric transcription factors has been noted for its frequent involvement in chromosomal translocations associated with leukemia. Using reverse transcriptase-polymerase chain reaction (RT-PCR) combined with nonisotopic RNase cleavage assay (NIRCA), we found point mutations of the AML1 gene in 8 of 160 leukem...

The AML1 gene encoding the DNA-binding a-subunit in the Runt domain family of heterodimeric transcription factors has been noted for its frequent involvement in chromosomal translocations associated with leukemia. Using reverse transcriptase-polymerase chain reaction (RT-PCR) combined with nonisotopic RNase cleavage assay (NIRCA), we found point mutations of the AML1 gene in 8 of 160 leukemia p...

The core binding factor (CBF) heterodimeric transcription factors comprised of AML/CBFA/PEBP2alpha/Runx and CBFbeta/PEBP2beta subunits are essential for differentiation of hematopoietic and bone cells, and their mutation is intimately related to the development of acute leukemias and cleidocranial dysplasia. Here, we present the crystal structures of the AML1/Runx-1/CBFalpha(Runt domain)-CBFbet...

The fusion transcript AML1/ETO was detected in the bone marrow of two t(8;21)-negative acute myelogenous leukemia (AML) patients by means of reverse transcription-polymerase chain reaction. This fusion transcript is identical to the one transcribed from the t(8;21) translocation base, as deduced from (a) the size and restriction pattern of the amplified DNA fragment and (b) the DNA sequence ana...

The 8;21 translocation, t(8;21)(q22;q22.3), is seen only in acute myelogenous leukemia and is characteristically associated with the M2 subtype. Subsequent to our identification of the t(8;21) breakpoint region on chromosome 21, we reported that the translocation results in the fusion of the AML1 gene on chromosome 21 with a novel gene on chromosome 8 which we called ETO (for eight twenty-one)....