Bortezomib suppresses self-renewal and leukemogenesis of leukemia stem cell by NF-ĸB-dependent inhibition of cyclin dependent kinase 6 in MLL-rearranged myeloid leukemia

Acute myeloid leukemia (AML) with chromosomal rearrangements involving the H3K4 methyltransferase mixed-lineage leukemia (MLL) is an aggressive subtype with low overall survival. MLL rearrangements rapidly transform hematological stem and progenitor cell (HSPC) to leukemia stem cell (LSC). Bortezomib (Velcade) is used widely in hematological malignancies. However, it is still unknown whether bortezomib possesses anti-self-renewal and anti-leukemogenesis of LSC in AML with MLL rearrangements. Here, we found that bortezomib inhibited cell proliferation, induced apoptosis, and decreased colony formation in leukemic cell lines, primary AML blasts, and MLL-AF9-transformed murine leukemic blasts. Besides, bortezomib reduced the frequency and function of LSC, inhibited the progression, and prolonged Examination of bortezomib-treated leukemia stem cells.