Chronic Myeloid Leukemia and BCR/ABL Signal Pathway Are Not Associated with AKT1 Pleckstrin Homology Domain(E17K) Mutations.

Abstract 4262

AKT1 E17K mutation was recently found in several human cancers. PI3K/AKT is one of major downstream signal pathways of BCR-ABL oncogene and essential for CML leukemogenesis and IM resistance. More recently, it has been shown that increased PI3K/AKT activity in CML contributes to the development of drug resistance of malignant cells and combination of PI3K/AKT pathway inhibitor and rapamycin can efficiently kill imatinib-resistant BCR-ABL-expressing cells, highlighting the potential of PI3K/AKT as the new targets for CML therapy. Considering the central role of AKT in CML, we performed a screening study to investigate the possible role of AKT1 E17K mutation in CML in the Chinese population. To study the frequency of AKT1 E17K mutation in CML patients in Chinese population as well as its possible relation to IM sensitivity, we recruited 86 patients with CML revealed the presence of Philadelphia chromosome at diagnosis. At molecular level, B2a2, B3a2, B2a3 and B3a3 were identified by RT-PCR in 41,43,1 and 1 cases, respectively. Molecular response to IM was evaluated by real-time PCR at 6 months and 12 months after IM administration. The CCR, MMR and CMR were achieved in 74, 39 and 27 cases, respectively. No AKT1 E17K mutation was found in all patients. We also studied the AKT1 E17K genotype in 7 CML patients at blast stage. The additional genetic abnormalities were summarized. For these patients, CD34+ leukemic cells were purified by FACS from PBMNCs before DNA extraction. Again, we failed to detect any AKT1 E17K mutant in this group of patients.