Significance of WT1 gene detection in the prognosis of acute myeloid leukemia patients with normal karyotype after hematopoietic stem cell transplantation

Abstract

Objective To investigate the monitoring significance of WT1 gene level in the prognosis of acute myeloid leukemia (AML) patients with normal karyotype after hematopoietic stem cell transplantation (HSCT). Methods The clinical data of 115 AML patients with normal karyotype who were treated with HSCT from July 2009 to March 2017 in the First Affiliated Hospital of Soochow University were retrospectively analyzed. The dynamic detection of bone marrow WT1 gene was carried out by using reverse transcription- polymerase chain reaction (RT-PCR). According to the relative expression level median of WT1 gene before transplantation, the whole patients were divided into the two groups (< median group and ≥ median group) for survival analysis. Results There were 52 males and 63 females in 115 patients. The average age was (39±10) years old. The median white blood cell count at initial diagnosis was 20.45×109/L [(0.5-355.9)×109/L], the ratio of blast cells in the bone marrow was 0.60±0.28, and the relative expression level median of WT1 gene was 87×104, while the median time of the follow-up was 24 (3-79) months. Among 115 patients, 19 cases relapsed. Remission group (96 cases) and relapse group (19 cases) were followed up. The WT1 gene level was monitored by using bone marrow puncture in 1 month, 3 months, 6 months, 12 months after transplantation. It was found that the WT1 gene relative expression level of relapse group was higher than that of remission group, and the differences between the two groups at 6 month-point [remission group (187±50)×104, relapse group (871±211)×104, t= 2.519, P= 0.014] and 12 month-point [remission group (51±9)×104, relapse group (1 797±312)×104, t= 4.000, P < 0.05] were statistically different. The overall survival (OS) rate of 2-year, progression-free survival rate in WT1 gene relative expression level < 87×104 group were higher than those in WT1 gene relative expression level ≥ 87×104 group, the relapse rate in WT1 gene relative expression level < 87×104 group was lower than that in WT1 gene relative expression level ≥ 87×104 group, and the differences were statistically different (all P < 0.05). Multivariate analysis showed that the level of WT1 gene at 12 months after transplantation was an independent factor affecting OS (HR = 4.12, P = 0.046) and PFS (HR = 5.95, P = 0.001). There were 19 cases of recurrence (16.5%), with a median relapsed time of 11 (1-60) months. When WT1 gene relative expression level was significantly increased in 19 patients, firstly immunosuppressive agents were reduced, of which 6 patients were not influenced by this intervention; in other 13 cases, only 5 cases were influenced by intervention. Conclusions For CN-AML patients, the expression level of WT1 gene before transplantation has a negative correlation with the prognosis. The expression level of WT1 gene at 12 months after transplantation is an independent factor for affecting the survival. The relapsed patients have a higher WT1 expression level, and clinical interventions for relapsed patients have a favorable effect. Key words: Gene, WT1; Hematopoietic stem cell transplantation; Leukemia, myeloid, acute; Prognosis