BCL2 Expression at Post-Induction and Complete Remission Impact Outcome in Acute Myeloid Leukemia.

Cristina Bilbao-Sieyro,Cristina Bilbao-Sieyro,Ruth Stuckey,María Nieves Sáez,María Teresa Gomez-Casares,Jesús María González Martín,Carlos Rodríguez-Medina,Guillermo Santana,Teresa Molero Labarta,Santiago Sánchez-Sosa,Elena González-Pérez,Rosa Fernández,Naylén Cruz-Cruz,Yanira Florido

doi:10.3390/diagnostics10121048

Abstract

Advances in acute myeloid leukemia (AML) genomics and targeted therapies include the recently approved BCL2 inhibitor venetoclax. The association between BCL2 expression and patient outcome was analyzed in a series of 176 consecutive AML patients at diagnosis (Dx), post-induction (PI), complete remission (CR) and relapse (RL). Levels increased significantly at relapse (mean 1.07 PI/0.96 CR vs. 2.17 RL, p = 0.05/p = 0.03). In multivariate analysis, high BCL2-Dx were marginally associated with worse progression-free survival, while high PI levels or at CR had an independent negative impact on outcome (PI: HR 1.58, p = 0.014; CR: HR 1.96, p = 0.008). This behavior of high PI or CR BCL2 levels and increased risk was maintained in a homogeneous patient subgroup of age <70 and intermediate cytogenetic risk (PI: HR 2.44, p = 0.037; CR: HR 2.71, p = 0.049). Finally, for this subgroup, high BCL2 at relapse indicated worse overall survival (OS, HR 1.15, p = 0.05). In conclusion, high BCL2 levels PI or at CR had an independent negative impact on patient outcome. Therefore, BCL2 expression is a dynamic marker that may be useful during AML patient follow up, and BCL2 levels at PI and/or CR may influence response to anti-BCL2 therapy.

Highlights

Advances in acute myeloid leukemia (AML) genomics have revealed the broad biological heterogeneity of the disease, leading to new risk stratifications in the pathology and the incorporation of targeted therapies for a more personalized management [1,2,3]
We studied the influence of BCL2 bone marrow expression on patient outcome in a consecutive series of 176 AML patients at diagnosis (Dx), and when possible, at post-induction (PI, when the patient recovers blood count, between days 21–28 after induction [8]); morphological complete remission (CR) (i.e.,
Analyzing the expression dynamics of the same patients at different time points (Supplementary Figure S2), compared to Dx, BCL2 levels showed a marked descent at PI (n = 86, mean Dx 1.64 vs. PI 0.97, p < 0.001) and when achieving CR (n = 64, Dx 1.57 vs. CR 0.95, p < 0.001; Supplementary Table S1), but raised again at RL compared to PI (n = 23, RL 2.17 vs. PI 1.07, p = 0.05) and CR (n = 20, RL 2.27 vs. CR 0.96, p = 0.03)

Summary

Introduction

Advances in acute myeloid leukemia (AML) genomics have revealed the broad biological heterogeneity of the disease, leading to new risk stratifications in the pathology and the incorporation of targeted therapies for a more personalized management [1,2,3]. The molecular characteristics of patients likely to respond to venetoclax remain to be determined To address this issue, we studied the influence of BCL2 bone marrow expression on patient outcome in a consecutive series of 176 AML patients at diagnosis (Dx), and when possible, at post-induction (PI, when the patient recovers blood count, between days 21–28 after induction [8]); morphological complete remission (CR) (i.e.,

Methods

Results

Conclusion