Can the Gene Expression Profile of Patients with Acute Myeloid Leukemia Predict Complete Remission Following Induction Therapy?

Abstract

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.

Biomarkers of Response to Venetoclax Therapy in Acute Myeloid Leukemia

“…Malignant blasts have the ability to evade apoptosis via the constitutively elevated expression of antiapoptotic proteins of the BCL-2 family. Molecular studies have confirmed these observations and demonstrated the prognostic impact of high levels of expression of BCL2, measured by immunohistochemistry [10] or mRNA quantification [11,12]. Moreover, high levels of BCL-2 family proteins are associated with resistance to chemotherapy [10,13,14].…”

“…The expression of other genes may also have prognostic value. In fact, several multi-gene scores have been developed to predict which AML patients, achieving complete remission (CR) in response to standard induction therapy, will have longer survival [12,40,41]. The application of these scores may help distinguish patients who will require a cell therapy-based approach from those who are chemosensitive and thus might avoid allogeneic hematopoietic stem cell transplantation (HSCT).…”