RESUMO
Recent advances in sequencing technologies and genomics have led to the development of several targeted therapies such as BCL2 and Bromodomain and extra-terminal (BET) protein inhibitors for a more personalized treatment of patients with acute myeloid leukemia (AML), yet the majority of patients still receive standard induction chemotherapy. The molecular profiles of patients who are likely to respond to induction therapy and novel directed therapies remain to be determined. The expression of AML-related genes that are targeted by novel therapies such as BCL2 and BRD4, as well as functionally related genes and associated epigenetic modulators (TET2, EZH2, ASXL1, MYC) were analyzed in a series of 176 consecutive AML patients at multiple points during the disease course - diagnosis (Dx), post-induction (PI), complete remission (CR) and relapse (RL) - and their relationship with clinical variables and outcome investigated. Higher TET2 expression was observed PI and at CR compared to Dx, with significantly superior TET2 expression after induction therapy in the group of patients who reached CR compared to those who did not. Thus, the upregulation of TET2 at PI may be a marker of CR in AML patients. On the other hand, cells with high levels of MYC and BCL2 may be vulnerable to BRD4 inhibition.
RESUMO
The search for useful molecular markers in the diagnosis of AML and in the follow-up of minimal residual disease (MRD) has been the focus of many recent studies. Previous research showed that, while normal bone marrow cells lack expression of renin, myeloid blasts have been reported to do so. The aim was to study the expression of the renin gene by the use of real-time quantitative PCR (RQ-PCR) at diagnosis in acute myeloid leukemia patients (AML) and to assess its possible relevance in the prognosis and outcome of such patients. This study analysed 76 samples from patients with AML, with follow-up of positive patients. Thirty-one patients (41%) were positive for renin gene expression at diagnosis. All renin-positive patients at diagnosis showed no expression during complete remission (CR), but expression recurred in those experiencing relapse and persisted when the disease was refractory to treatment. Although the results suggest that the sub-group of renin-positive AML patients might have a worse outcome and a higher relapse rate (at 5 years, the projected rate of disease-free survival was 18.5 +/- 9.8% for renin-positive and 23.5 +/- 8.8% for renin-negative patients), no significant differences were found. It is believed that further studies should aim to validate whether such a difference exists, using a much larger and homogeneus group of patients.
