Yan Liu1,2,3,4,5, Zhiheng Cheng6, Qihui Li3, Yifan Pang7, Longzhen Cui2, Tingting Qian1,4, Liang Quan1,4, Yifeng Dai8, Yang Jiao9, Zhihui Zhang10, Xu Ye1, Jinlong Shi11, Lin Fu1,4,5. 1. Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China. 2. Translational Medicine Center, Huaihe Hospital of Henan University, Kaifeng 475000, China. 3. Department of Hematology and Lymphoma Research Center, Peking University, Third Hospital, Beijing 100191, China. 4. Translational Medicine Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China. 5. Department of Hematology, Huaihe Hospital of Henan University, Kaifeng 475000, China. 6. Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 7. Department of Medicine, William Beaumont Hospital, Royal Oak, MI 48073, USA. 8. Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 9. Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou 310058, China. 10. Department of Stomatology, Peking University Third Hospital, Beijing 100191, China. 11. Department of Medical Big Data, Chinese PLA General Hospital, Beijing 100853, China.
Abstract
BACKGROUND: Acute myeloid leukemia (AML) is a highly heterogenous hematological malignancy and its prognostication depends on the genetic mutation and expression profile of each patient. Pantothenate kinase (PANK) is a regulatory enzyme that controls coenzyme A (CoA) biosynthesis. It has four isoforms encoded by PANK1-4, respectively. Whether the expression of the PANK family has prognostic significance in AML remains unclear. METHODS: We screened The Cancer Genome Atlas database for AML patients with complete PANK1-4 expression data. Eighty-four AML patients met the criteria and were included in this study. Clinical characteristics at diagnosis, including peripheral blood (PB) white blood cell counts (WBC), blast percentages in PB and bone marrow (BM), French-American-British (FAB) subtypes and the frequencies of common genetic mutations were described. Survival was estimated using the Kaplan-Meier method and the log-rank test. Multivariate Cox proportional hazard models were constructed for event-free survival (EFS) and overall survival (OS), using a limited backward elimination procedure. RESULTS: Patients with high PANK2 expression had significantly longer event-free survival (EFS) and overall survival (OS) than patients with low PANK2 expression (P=0.007, P=0.016, respectively), whereas patients with high PANK4 expression had shorter EFS and OS than patients with low PANK4 expression (P=0.022, P=0.015, respectively). Multivariate analysis confirmed that high PANK4 expression was an independent risk factor for EFS and OS (both P<0.05). CONCLUSIONS: Our study suggested that high PANK2 expression might have favorable effects on AML, while high PANK4 expression was indicative of poor prognosis.
BACKGROUND: Acute myeloid leukemia (AML) is a highly heterogenous hematological malignancy and its prognostication depends on the genetic mutation and expression profile of each patient. Pantothenate kinase (PANK) is a regulatory enzyme that controls coenzyme A (CoA) biosynthesis. It has four isoforms encoded by PANK1-4, respectively. Whether the expression of the PANK family has prognostic significance in AML remains unclear. METHODS: We screened The Cancer Genome Atlas database for AML patients with complete PANK1-4 expression data. Eighty-four AML patients met the criteria and were included in this study. Clinical characteristics at diagnosis, including peripheral blood (PB) white blood cell counts (WBC), blast percentages in PB and bone marrow (BM), French-American-British (FAB) subtypes and the frequencies of common genetic mutations were described. Survival was estimated using the Kaplan-Meier method and the log-rank test. Multivariate Cox proportional hazard models were constructed for event-free survival (EFS) and overall survival (OS), using a limited backward elimination procedure. RESULTS: Patients with high PANK2 expression had significantly longer event-free survival (EFS) and overall survival (OS) than patients with low PANK2 expression (P=0.007, P=0.016, respectively), whereas patients with high PANK4 expression had shorter EFS and OS than patients with low PANK4 expression (P=0.022, P=0.015, respectively). Multivariate analysis confirmed that high PANK4 expression was an independent risk factor for EFS and OS (both P<0.05). CONCLUSIONS: Our study suggested that high PANK2 expression might have favorable effects on AML, while high PANK4 expression was indicative of poor prognosis.
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