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J Cancer 2022; 13(4):1356-1362. doi:10.7150/jca.57457 This issue Cite

Research Paper

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

Santiago Sánchez-Sosa^1,2#, Carlos Rodríguez-Medina^1#, Ruth Stuckey¹, Yanira Florido¹, Guillermo Santana¹, Jesús María González Martín³, Naylén Cruz-Cruz¹, Melissa Torres-Ochando¹, Rosa Fernández⁴, Nuria Sánchez-Farías¹, Antonia Cionfrini¹, Teresa Molero Labarta^1,2, María Teresa Gomez-Casares^1,2, Cristina Bilbao-Sieyro^1,5✉

1. Hematology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain.
2. Medical Science Department, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain.
3. Unidad de Investigación, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain.
4. Hematology Department, Complejo Hospitalario Universitario Insular Materno Infantil, Las Palmas de Gran Canaria, Spain.
5. Morphology Department, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain.
#These authors have contributed equally to this work.

✉ Corresponding author: Dr. Cristina Bilbao-Sieyro, Molecular Biology Group, Hematology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Barranco de La Ballena S/N, Las Palmas de Gran Canaria, 35010, Spain. Tel: 0034 928 449420; Fax: 0034 928 449827; Email: bilbaocristinacom. More

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.

Keywords: acute myeloid leukemia, biomarkers, patient outcome, induction therapy, molecular diagnostics

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