The Platelet Isoform of Phosphofructokinase in Acute Myeloid Leukemia: Clinical Relevance and Prognostic Implication

Background: Phosphofructokinase (PFK), a key enzyme of the glycolytic pathway, has L (liver), M (muscle), and P (platelet) isoforms with different tissue distributions. The Platelet Isoform of PFK (PFKP) plays an important role in regulating aerobic glycolysis and macromolecular biosynthesis to support cell growth. Up-regulation of PFKP is associated with progression and metastasis of varied kinds of solid organ tumor. However, less is known about the association between PFKP and hematology malignancy. Here, we investigated the role of PFKP in acute myeloid leukemia (AML).

Methods: To characterize PFKP mRNA expression in AML, we performed qRT-PCR on bone marrow cells (BMCs) from 55 newly diagnosed AML patients with the median age of 47 years (range 16-82 years). The FAB type is M0 (2/55), M1 (3/55), M2 (15/55), M3 (11/55), M4 (11/55) and M5 (11/55). Two patients were diagnosed with myelodysplastic syndromes related AML. We screened for mutations in a selected panel of genes (NPM1, CEPBA, FLT3, KIT, WT1 and TP53), based on which patients were further categorized into standard (19/55), intermediate (21/55) and poor (15/55) cytogenetic risk groups. Patients were categorized into PFKP_high and PFKP_low groups according to the median mRNA expression of PFKP. Complete remission (CR) rate was compared between two groups after 1 cycle and 4 cycles of chemotherapy. One year-relapse rate, overall survival rate (OS) and disease free survival rate (DFS) was also compared between PFKP_high and PFKP_low groups.

Results:PFKP mRNA expression of AML patients was significantly higher than that of the normal control (P<0.05). PFKP expression in different cytogenetic risk groups were evaluated and the result showed that the mRNA expression in poor risk group was much higher than that in standard or intermediate group (P<0.05). According to the median mRNA expression of PFKP, patients were categorized into PFKP_high (28/55) and PFKP_low (27/55) groups. The CR rate after the first cycle of treatment was higher in PFKP_low group, but did not differ significantly after another 3 cycles of chemotherapy were finished. PFKP mRNA expression was decreased after patients received CR (P<0.05). In 32 out of 55 patients, autologous hematopoietic stem cell transplantation (HSCT) (N=20) or allogeneic HSCT (N=12) was performed after 4 cycles of chemotherapy. In 20 patients post auto-HSCT, 1 year-relapse rate was higher and OS and DFS was decreased significantly in PFKP_highgroup compared to PFKP_low group. However, results showed no difference between two groups for patients post allo-HSCT.

Conclusions:PFKP expressions were increased in AML especially patients in poor cytogenetic risk group. PFKP might be a prognostic factor of poor clinical outcome of AML.