General AML

The role of galectin-3 in newly diagnosed APL patients treated with ATRA and ATO based regimens - A Chinese Study

Galectin-3 (gal-3) is a member of the β-galactoside-specific lectin family with pleiotropic biological functions. Gal-3 has roles in cell differentiation, apoptosis, and drug resistance, and its expression has been shown to be associated with poor prognosis in Acute Myeloid Leukemia (AML) patients.1 However, its role in the AML subtype Acute Promyelocytic Leukemia (APL) is not clear.

Gao et al., from the Binzhou Medical University Hospital, China, investigated the concentrations of serum gal-3 and its effect on the outcomes of APL patients.2 The results of the study were published ahead of print in the Annals of Hematology on 25th February 2017.

In this study, the authors retrospectively studied 108 newly diagnosed APL patients (median age = 40.1 years) with complete clinical data at the Binzhou Medical University Hospital from July 2007–July 2014 and treated with All Trans Retinoic Acid (ATRA) in combination with Arsenic Trioxide (ATO).

The key results of the study were:
  • Median gal-3 protein level in APL patients and healthy controls; 4.09 ng/ml (range, 0.42–12.32 ng/ml) vs 1.67 ng/ml (range, 0.29–8.17 ng/ml), P < 0.001
  • Older age (P < 0.001), history of psoriasis (P = 0.036), CD34 expression (P = 0.004), and coagulopathy (P = 0.036) were associated with high gal-3 levels (> 4.09 ng/ml)
  • Overall Survival (OS) was shorter in patients with high gal-3 levels (> 4.09 ng/ml, n = 49) compared to patients with low gal-3 levels (< 4.09 ng/ml, n = 57); P = 0.028
  • Relapse Free Survival (RFS) was shorter in patients with high gal-3 levels compared to patients with low gal-3 levels; P = 0.001
  • Cumulative Incidence of Relapse (CIR) was higher in patients with high gal-3 levels compared patients with low gal-3 levels; P = 0.02
  • Higher gal-3 level was an independent unfavorable factor for RFS; HR = 3.852, P = 0.049

In summation, this is the first study to reveal that serum gal-3 levels may be an independent unfavorable prognostic factor for RFS in APL patients.

The authors concluded by suggesting that gal-3 may become a reliable biomarker to predict prognosis in APL patients. They further suggested that due to retrospective nature of their study, further clinical studies are required to confirm the findings of their study.

Abstract

Increased galectin-3 expression has been currently showed to be associated with poor prognosis in some hematological malignancies, such as acute myeloid leukemia, diffuse large B cell lymphoma. However, little is known about the clinical significance of galectin-3 in patients with acute promyelocytic leukemia (APL). We investigated the concentration of serum galectin-3 and characterized the relationship between galectin-3 and outcome in patients with APL. Higher galectin-3 levels were detected in patients with APL compared with the healthy controls (p < 0.001). Higher galectin-3 levels were closely associated with older ages (p < 0.001), the medical history of psoriasis (p = 0.036), coagulopathy (p = 0.042), and CD34 expression (p = 0.004). Compared with patients with lower galectin-3 levels, those with higher galectin-3 levels had significant shorter overall survival (p = 0.028) and relapse-free survival (p = 0.001). Multivariate analysis showed that serum galectin-3 was an independent unfavorable factor for relapse-free survival in patients with APL treated with all-trans retinoic acid and arsenic trioxide-based frontline therapy. Clinical impact of galectin-3 should be further investigated in patients with APL.

References
  1. Cheng C.L.et al. Higher bone marrow LGALS3 expression is an independent unfavorable prognostic factor for overall survival in patients with acute myeloid leukemia. Blood. 2013 Apr 18; 121(16): 3172–80. DOI: 1182/blood-2012-07-443762. Epub 2013 Feb 28.
  2. Gao N.et al. Clinical impact of galectin-3 in newly diagnosed t (15;17)(q22;q21)/PML-RARa acute promyelocytic leukemia treated with all-trans retinoic acid and arsenic trioxide-based regimens. Ann Hematol. 2017 Feb 25. DOI: 1007/s00277-017-2948-3. [Epub ahead of print].