Education session on acute myeloid leukemia (AML)

Two main subjects were covered in the Friday morning session:
1) the concept of leukemic stem cells to be reached by targeted therapeutics,
2) the new targeted therapies available in AML.

AML stem cells have similar characteristics to normal stem cells and also able to self renew. It is a major task to identify genes differentially expressed in leukemic stem cells when compared to normal stem cells. Dr Brian Huntly described the promising effects of inhibitors such as rapamycin and parthenolide to selectively inhibit leukemic stem cells via mTOR and NFKB inhibition, respectively.

New targeted therapyin AML can be directed against several components:

• surface antigens such as CD33; the use of anti CD33 antibodies (Mylotarg) in different trials, often in combination with chemotherapy, was described by Dr Alan Burnett.
• drug resistance due to P glycoprotein expression; inhibitors such as Zosuquidar are used in ongoing trials.
• signaling pathways activated in AML; inhibitors of FLT3 (PKC412, CEP7010), of RAS family proteins (FTI), of the proteasome (bortezomid) are being developed and tested
• anti-angiogenic agents, such as inhibitors of VEGF receptor are also being studied
• epigenetic events.

Dr Amadori described these different therapies and their possible use in older adults in AML in addition to chemotherapy.