The Role of Galectin-3 Expression in Acute Myeloid Leukemia and Its Clinical Implication
Date Issued
2012
Date
2012
Author(s)
Cheng, Chieh-Lung
Abstract
Background
Galectin-3, a β-galactoside-binding lectin, plays an important role in cancer cell progression, adhesion, apoptosis, transformation, angiogenesis and metastasis. A lot of researches also demonstrated an important role of galectin-3 expression in several types of malignancies. However, the studies concerning clinical implications of galectin-3 expression in patients with acute myeloid leukemia (AML) are scarce.
Aims
In this study we aimed to determine the clinical implication of the expression of LGALS3, the gene encoding galectin-3, in adult de novo non-M3 AML patients.
Methods
We investigated the expression of LGALS3 in the bone marrow (BM) by reverse-transcriptase real-time polymerase chain reaction in a test cohort consisting of 280 adults 15 years of age or older with newly diagnosed de novo non-M3 AML at the National Taiwan University Hospital and correlated the results with clinical features and outcomes of the patients. The prognostic impact of BM LGALS3 expression was also validated in an independent cohort comprised 42 de novo non-M3 AML patients.
Results
Among 280 patients, those with higher BM LGALS3 expression were older (P<0.001), more frequently had French-American-British (FAB) M4 and M5 subtypes (both P=0.003), and CD14 expression on leukemic cells (P=0.009), but less commonly had FAB M1 subtype (P<0.001). In addition, higher LGALS3 expression was closely associated with PTPN11 mutation but negatively associated with FLT3-ITD and CEBPA mutation. There was no correlation between the cytogenetic abnormalities and BM LGALS3 expression. Survival analysis was performed in 211 non-M3 AML patients who received standard intensive cure-intent chemotherapy. Patients with higher BM LGALS3 expression, compared to those with lower expression, had lower CR rates (61.5% vs. 82.5%, P=0.001) and higher primary refractory rates (23.1% vs. 10.8%, P=0.023). With a median follow-up time of 69.5 months, patients with higher BM LGALS3 expression had a shorter overall survival than those with lower expression (median 16.3 months vs. 39.8 months, P=0.02). Moreover, multivariate analysis demonstrated that higher BM LGALS3 expression was an independent poor prognostic factor for overall survival among total patients and patients with normal karyotype. The unfavorable prognostic impact of higher BM LGALS3 expression was also confirmed in the independent validation cohort. A scoring system incorporating higher BM LGALS3 expression and eight other prognostic factors, including age, white blood cell count, cytogenetics, NPM1/FLT3-ITD, MLL-PTD, CEBPAdouble-mut and mutations of AML1/RUNX1 and WT1, into survival analysis was proved to be very useful to stratify AML patients into different prognostic groups (P<0.001).
Conclusions
Our research provides evidences that BM LGALS3 expression is associated with distinct biologic and clinical characteristics in AML. Higher BM LGALS3 expression is significantly correlated with poor prognosis in AML patients. BM LGALS3 expression may serve as a new biomarker to predict clinical outcome. Galectin-3 may be a potential target for the treatment of AML patients with higher expression of this protein.
Subjects
Galectin-3
LGALS3
Acute myeloid leukemia
Prognosis
SDGs
Type
thesis
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