Investigations revealed that treatment with the newly synthesized drug analogue SH-03[{(7S,7aR,13aS)-9,10-dimethoxy-3,3-dimethyl-7,7a,13,13atetrahydro-3H-chromeno[3,4-b]pyrano[2,3-h]chromen-7-ol}] could induce AGO2-mediated apoptosis in myeloid leukaemia cells via intrinsic apoptotic pathways independent of Dicer.
Further investigations revealed that knock-down of AGO2 by custom-made AGO2 siRNA in HEK-293 cells resulted in silencing of the expression of target genes vascular endothelial growth factor A and histone deacetylase 2, which are known to be involved in the development of myeloid leukaemia.
These findings suggest that inv(2)(p23q13)/RABBP2-ALK defines a small subset of myeloid leukemia characterized by differentiation to monocytes and sharing features of myelodysplastic syndrome/myeloproliferative neoplasm.
Although ASXL1 mutations are frequently found in human diseases, including myeloid leukemia, the cell proliferation-associated function of ASXL1 is largely unknown.
To identify acquired somatic mutations associated with myeloid transformation in patients with GATA2 mutations, we sequenced the region of the ASXL1 gene previously associated with transformation from myelodysplasia to myeloid leukemia.
The ufo protein (also termed axl) is a member of a new family of receptor tyrosine kinases and is encoded by a transforming gene that was initially isolated from primary human myeloid leukemia cells by DNA-mediated transformation of NIH/3T3 cells.
Evi9, a common site of retroviral integration in BXH2 murine myeloid leukemias, encodes a C2H2 zinc finger protein and is overexpressed in these leukemic cells.
The presence of bcl-2 in myeloid leukemias has been associated with a decrease in therapy-induced apoptosis, reduced patient survival and in vitro autonomous growth of leukemic cells.
We have therefore analyzed 21 bone marrow aspirates from untreated childhood acute lymphoblastic leukaemia and 2 from myeloid leukaemia for mutations in box and bcl-2.