The serine/threonine kinase AKT1 (v-akt murine thymoma viral oncogene homologue 1) has a central role in the signaling of growth factors and other stimuli, leading to diverse cellular functions including cell survival, proliferation, growth and metabolism (reviewed in Vivanco & Sawyers, 2002). Furthermore, the deregulation of the phosphoinositide-3-kinase (PI3K)/AKT pathway is a common mechanism for transformation and by far the most frequently mutated component of this pathway is the tumour suppressor PTEN (Manning & Cantley, 2007). The original description of AKT1 involved virally induced carcinogenesis resulting from a constitutively active form of v-akt (Manning & Cantley, 2007). A recent report identified a recurrent mutation in the pleckstrin homology (PH) domain of AKT1 that results in a glutamic acid to lysine substitution at amino acid 17 (E17K) in breast cancer (8%), ovarian cancer (2%) and colorectal cancer (6%) (Carpten et al, 2007). The mutation was shown to activate AKT1 and lead to cellular transformation and the development of leukaemia in mice. In addition, the PI3K/AKT pathway plays an important role in both chronic and acute leukaemia pathogenesis, and a growing number of compounds have been developed to target the PI3K/AKT. Therefore, we investigated a possible role of AKT1 E17K mutation in a large cohort of patients with chronic lymphocytic leukaemia (CLL) and acute myeloid leukaemia (AML). We studied the AKT1 E17K genotype in 106 CLL patients and 95 patients with AML (Table I). DNA was extracted using Trizol or Qiagen and the following primer sequences were used to generate the DNA product (AKT1 x3 FWD ACATCTGTCCTGGCACAC; AKT1 x3 REV GCCAGTGCTTGTTGCTTG) (Carpten et al, 2007). Polymerase chain reaction (PCR) amplifications were performed using the Gene Amp PCR core reagent kit (Applied Biosystems, Foster City, CA, USA). The final concentrations of the PCR reagents were 1× PCR Gold buffer, 2 mmol/l MgCl2, 200 μmol/l of each dNTP, 400 nmol/l each forward and reverse primer, 1·25 U of AmpliTaq Gold DNA polymerase enzyme, and 200 ng of genomic DNA in a 50-μl reaction volume. Thermal cycler conditions were: 95°C for 5 min, 35 cycles of 94°C for 30 s, 60°C for 30 s, 72°C for 1 min, and a final extension at 72°C for 10 min. The PCR products were analysed by automated fluorescent sequencing using Big Dye Terminator Kit and ABI 3100 sequencer (Applied Biosystems). The sequences were analysed visually and with the Staden package (available at http://staden.sourceforge.net). The AKT1 E17K mutation was not found in any of the 204 leukaemia patients, suggesting that the mutation is unlikely to play a significant role in transformation or disease modification in CLL and AML. Similar to the results reported here, a very recent report did not identify the AKT1 E17K mutation in 49 AML patients (Tibes et al, 2008). While the signalling molecules upstream of AKT1 are commonly mutated in AML (FLT3, RAS, and KIT), AKT1 appears to be activated by other causes than a mutation of the PH domain. AKT1 has recently been shown to be up-regulated in CLL cases with 13q deletion (Kienle et al, 2007), and AKT1 has been suggested to be an important component of the survival pathway that can be activated in CLL B cells by antigen stimulation (Longo et al, 2007). PTEN, the negative regulator of AKT1, has been implicated in a number of epithelial cancers where it is inactivated by mutation (Vivanco & Sawyers, 2002). Inactivation of PTEN by mutations were not found in a small series of patient material from CLL, but PTEN protein expression was reduced or not detected in 48% of B-CLL patients (Leupin et al, 2003). Similarly, PTEN mutations seem to be rare events in AML (Liu et al, 2000). While it is currently unclear how AKT1 is deregulated in these leukaemias, one could speculate that AKT1 may be active in CLL because of BCR stimulation. In AML, AKT1 may be activated by mutated kinases (e.g. FLT3 activated by either an internal tandem duplication or a tyrosine kinase domain mutation) that could render the mutational activation of AKT1 itself dispensable. This work was supported in part by grants from the Else-Kröner-Fresenius-Stiftung (P32/2004) and German José Carreras Leukaemia Foundation grants (DJCLS R06/28v).