Interleukin-8 is not a predictive biomarker for the development of the acute promyelocytic leukemia differentiation syndrome

Luciana Yamamoto De Almeida,Sarah Cristina Bassi,Priscila Santos Scheucher,Diego Antonio Pereira-Martins,Ana Paula Lange,Ana Sílvia Gouvêa Lima,Eduardo Magalhães Rego,Márcia Sueli Baggio,Luisa Corrêa De Araujo Koury

doi:10.1186/s12885-020-07330-1

Luciana Yamamoto De Almeida, Sarah Cristina Bassi + Show 7 more

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https://doi.org/10.1186/s12885-020-07330-1

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Abstract

BackgroundDifferentiation syndrome (DS) is the main life-threatening adverse event that occurs in acute promyelocytic leukemia (APL) patients treated with all-trans retinoic acid (ATRA). Cytokine imbalances have been reported to play role during the developing of acute promyelocytic leukemia differentiation syndrome (APL-DS). However, the relationship between the plasma cytokine levels and their prognostic value for the prediction of DS developing in patients with APL during the treatment with ATRA and anthracyclines has not been previously reported.MethodsIn this study, we followed an APL cohort (n = 17) over 7 days of ATRA therapy in DS (n = 6) and non-DS groups (n = 11). Interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p70 and TNF-α were measured in the peripheral blood plasma from 17 patients with APL and 11 healthy adult controls by using the cytometric bead array method.ResultsIn non-DS patients, IL-8 plasma levels were significantly reduced in the seventh day of ATRA treatment (34.16; 6.99 to 147.11 pg mL− 1 in D0 vs. 10.9; 0 to 26.81 pg mL− 1 in D7; p = 0.02) whereas their levels did not discriminate between DS and non-DS development during the entire induction period (all p > 0.05 in D0, D3, and D7). No significant differences were found in IL-6 levels between groups (p > 0.05 in D0-D7). Other cytokines tested were all undetectable in patients with APL or healthy controls.ConclusionsWe demonstrated that the modulation of IL-8 following ATRA treatment may occur regardless of the development of DS and, therefore, does not appear to be a predictive biomarker to monitor the APL-DS.

Highlights

Differentiation syndrome (DS) is the main life-threatening adverse event that occurs in acute promyelocytic leukemia (APL) patients treated with all-trans retinoic acid (ATRA)
Differentiation syndrome (DS) is a life-threatening adverse event that occurs in approximately 20–25% of patients with acute promyelocytic leukemia (APL) undergoing induction therapy with all-trans retinoic acid (ATRA) [1, 2]
The ATRA-differentiating APL cells have increased ability to migrate from the blood flow into the tissues by upregulating molecules involved in cell adhesion (e.g.: ICAM: Intercellular Adhesion Molecule-1 and 2) and migration (e.g.: E-selectin and β2-integrin) [5, 8]

Summary

Introduction

Differentiation syndrome (DS) is the main life-threatening adverse event that occurs in acute promyelocytic leukemia (APL) patients treated with all-trans retinoic acid (ATRA). Cytokine imbalances have been reported to play role during the developing of acute promyelocytic leukemia differentiation syndrome (APL-DS). The relationship between the plasma cytokine levels and their prognostic value for the prediction of DS developing in patients with APL during the treatment with ATRA and anthracyclines has not been previously reported. Differentiation syndrome (DS) is a life-threatening adverse event that occurs in approximately 20–25% of patients with acute promyelocytic leukemia (APL) undergoing induction therapy with all-trans retinoic acid (ATRA) [1, 2]. It was experimentally demonstrated that increased expression of ICAM-1 on the lung of NOD/scid mice after ATRA therapy is important for the pulmonary infiltration of APL cells [10]. The IL-8 receptor CXCR2 is an adverse prognostic factor in AML and its inhibition decreases the proliferation of AML cell lines and primary samples [14]

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