Vol 44, No 2 (2013)
Prace poglądowe / Reviews
Published online: 2013-04-01

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Targeted therapy in acute myeloid leukemia

Jerzy Hołowiecki1, Aleksandra Hołowiecka2
DOI: 10.1016/j.achaem.2013.02.008
Acta Haematol Pol 2013;44(2):85-92.


Acute myeloid leukaemia – AML is a heterogeneous group of diseases, with different molecular characteristics and different prognosis. The results obtained using universal standard polychemotherapy are rather poor and there is a need for new drugs hitting the molecular targets specific for particular AML subtypes. Over the course of the last two decades a variety of such compounds have been developed in preclinical and clinical studies. Among monoclonal antibodies only the conjugate of anti-CD33 MoAb as a carrier with cytotoxic calichemicin (GO), was found effective mainly in CBF AML's. Much attention has been paid to FLT3 inhibitors. Mutations in the gene encoding FMS-like tyrosine kinase (FLT3) are present in 30% of AML cases and have a deleterious impact on prognosis. Eight inhibitors: Nidostaurin, Leustartinib, Sorafenib, Sanaksanit, Sunitinib, KW2449, Tandutynib and the most promising AC220, are in clinical trials phase I III. Extended studies of multikinase inhibitor Sorafenib appeared helpful in understanding major reasons of limited efficacy of monotherapy with FLT3 blockers. After initiation of treatment these drugs produce an excellent but only transient response resulting in AML blast clearance from the bone marrow. However, after few weeks an increasing resistance to treatment develops caused by generation of new mutations and selection of resistant clones. To solve this problem different combinations of drugs are currently a subject of preclinical and clinical studies.

Concerning other targets and agents the following appear important: blockers of CXCR4-SDF1 binding which is essential for AML blasts proliferation and survival (preliksafor, panobinostat, specyfic MoAb), agents influencing NF-κB (bortezomibe, parthenoide) and epigenetic drugs (azacytidine, decytabine).

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