Polo-like Kinase 4: the Variation During Therapy and its Relation to Treatment Response and Prognostic Risk Stratification in Childhood Acute Lymphoblastic Leukemia Patients

Abstract

Polo-like kinase 4 (PLK4) plays an essential role in the tumorigenesis of some blood malignancies; consequently, we hypothesized that PLK4 might serve as a potential biomarker in childhood acute lymphoblastic leukemia (ALL) patients. Therefore, this study investigated the expression of PLK4 and its clinical relevance in childhood ALL patients. Bone marrow specimens were collected from 95 childhood ALL patients and 20 primary immune thrombocytopenia patients (as controls), and their PLK4 expression (reverse transcription-quantitative polymerase chain reaction) was measured after enrollment. Besides, the PLK4 expression in childhood ALL patients was also determined at day 15 after the initiation of induction therapy (D15). PLK4 was increased in childhood ALL patients compared with controls (2.830 (interquartile range (IQR): 1.890-3.660) versus 0.976 (IQR: 0.670-1.288), P ≤0.001). PLK4 at diagnosis was elevated in T cell acute lymphoblastic leukemia patients than in B cell acute lymphoblastic leukemia patients ( P =0.027). Besides, PLK4 at diagnosis was positively linked with the Chinese Medical Association risk stratification ( P =0.016), but not with prednisone response ( P =0.077) or bone marrow response ( P =0.083). In addition, PLK4 was decreased at D15 after treatment compared with at diagnosis ( P ≤0.001). Interestingly, PLK4 at D15 (P=0.033) was elevated in T cell acute lymphoblastic leukemia patients than in B cell acute lymphoblastic leukemia patients. Furthermore, increased PLK4 at D15 was associated with poor prednisone response ( P =0.018), poor bone marrow response ( P =0.034), and increased the Chinese Medical Association risk stratification ( P =0.015). In terms of prognosis, high PLK4 was associated with shorter event-free survival ( P =0.020), whereas it was not related to the overall survival ( P =0.135). In conclusion, PLK4 has the potential as a biomarker for treatment response and prognostic risk stratification of childhood ALL patients.

FIGURE 1

PLK4 was upregulated in childhood ALL patients than controls. Comparison of PLK4 expression in childhood ALL patients and controls (A). The value of PLK4 in distinguishing childhood ALL patients from controls (B).ALL indicates acute lymphoblastic leukemia; PLK4, polo-like kinase 4.

FIGURE 2

PLK4 correlated with treatment response and risk stratification in childhood ALL patients. Association of PLK4 at diagnosis with prednisone response (A), bone marrow response (B), CMA risk stratification, and (C) in childhood ALL patients. Change of PLK4 from diagnosis to D15 after treatment in childhood ALL patients (D). Correlation of PLK4 at D15 after treatment with prednisone response (E), bone marrow response (F), CMA risk stratification, and (G) in childhood ALL patients. ALL indicates acute lymphoblastic leukemia; CMA, Chinese Medical Association; PLK4, polo-like kinase 4.

FIGURE 3

PLK4 high was related to shortened EFS in childhood ALL patients. Correlation of PLK4 with EFS (A) and OS (B) in childhood ALL patients. EFS indicates event-free survival; OS, overall survival; PLK4, polo-like kinase 4.