Generally, acute myeloid<unk>  is treated using chemotherapy consisting of an induction phase and consolidation phase (Dohner et al., 2009). Patients may also consider hematopoietic stem cell transplantation as a second mode of tackling the cancer. The most novel research is being done in tyrosine kinase inhibitors; however M2 acute myeloid<unk>  treatment research involves molecules that inhibit the fusion oncoprotein AML1-ETO. Therefore, in terms of M2 subtype acute myeloid<unk> , the most prominent target is the abnormal AML1-ETO fusion protein. Similarly, chronic myeloid<unk>  (CML) is comparable to acute myeloid<unk>  M2 because it also forms a fusion oncoprotein – BCR-Abl. The developed tyrosine kinase inhibitor, imatinib mesylate, has had a tremendous effect on stopping cancer progression in the majority of chronic myeloid<unk>  patients. BCR-Abl is constitutively active due chromosome translocation; therefore it over-phosphorylates the tyrosine kinase. Imatinib mesylate works to block BCR-Abl's activity by blocking the active kinase domain (Fava et al., 2011). Celastrol is a compound extracted from Tripterygium wilfordii that has anti-cancer properties. It was found to inhibit cell proliferation through the down regulation of AML1-ETO fusion oncoprotein. Celastrol inhibits the fusion oncoprotein by inducing mitochondrial instability and initiating caspase activity. The decrease of AML1-ETO also results in lower levels of C-KIT kinases, Akt/PKB, STAT3, and Erk1/2 – all of which are involved in cell signaling and gene transcription. Histone deacetylase inhibitors such as valproic acid (VPA), vorinostat, and all-trans retinoic acid (ATRA) are effective in targeting acute myeloid<unk>  with the AML1-ETO fusion protein. The HDAC inhibitors are known to induce apoptosis through accumulation of DNA damage, inhibition of DNA repair, and activation of caspases. These inhibitors are extra sensitive to the fusion proteins. Vorinostat has been proven to cause a greater accumulation of DNA damage in fusion protein expressing cells and is directly correlated with the reduction of DNA repair enzymes (Garcia et al., 2008). Romidepsin, a drug in phase two clinical trials, has demonstrated higher efficacy in patients with AML1-ETO fusion protein<unk>  (Odenike et al., 2008). Although many clinical evaluations have proven HDAC inhibitors have a promising effect on M2 subtype acute myeloid<unk> , it has not been approved as an official treatment. In t(6;9) acute myeloid<unk> , FLT3-ITD and the DEK-NUP214 protein are potential targets for treatment. Sorafenib is a kinase inhibitor used as a treatment for kidney and liver cancer. The kinase inhibitor blocks serine-threonine kinase RAF-1 as well as FLT-ITD (Kindler, 2010). The drug has been proven to be effective in reducing FLT3-ITD overexpression (Metzelder et al., 2009). In patients with DEK-NUP214, it was found that the fusion oncoprotein caused an upregulation of mTORC1 (Sanden et al., 2013). Thus, a mTORC inhibitor could be a potential treatment.
Acute myeloblastic leukemia with maturation
Acute myeloblastic leukemia without maturation
B-cell prolymphocytic leukemia
Minimally differentiated acute myeloblastic leukemia
Acute megakaryoblastic leukemia
Precursor B-cell lymphoblastic leukemia
Prolymphocytic leukemia
T-cell prolymphocytic leukemia