title: CXCR4 Overexpression is a Poor Prognostic Factor in Pediatric Acute Myeloid Leukemia With Low Risk: A Report From the Japanese Pediatric Leukemia/Lymphoma Study Group.
abstract: Overexpression of CXC chemokine receptor 4 (CXCR4+) is a poor prognostic factor in adult acute myeloid leukemia (AML); however, its prognostic significance in pediatric AML is unclear.
  
  
  
  This retrospective study examined the prognostic significance of CXCR4+ in pediatric AML patients enrolled in the Japanese Pediatric Leukemia/Lymphoma Study Group AML-05 study.
  
  
  
  In the total cohort (n = 248), no significant differences were observed between CXCR4+ patients (n = 81) and CXCR4- patients (n = 167) in terms of 3-year overall survival (OS) (69.4% vs. 75.2%, P = 0.44). However, there was a significant difference in 3-year OS between CXCR4+ and CXCR4- patients in the low-risk (LR) group (n = 93; 79.2% vs. 98.3%, P = 0.007). CXCR4+ patients in the t(8;21) AML without KIT mutation group had a significantly worse 3-year OS than CXCR4- patients (n = 44; 76.1% vs. 100.0%, P = 0.01). Multivariate Cox regression analysis identified CXCR4+ as a poor prognostic factor for OS in LR AML patients (hazard ratio, 11.47; P = 0.01). Consistent with the data for survival analysis, CXCR4+ patients in the t(8;21) AML group had a higher incidence of splenomegaly than CXCR4- patients (25.9% vs. 5.9%, P = 0.03).
  
  
  
  These results suggest that CXCR4+ is a poor prognostic factor for LR patients, particularly t(8;21) patients without KIT mutation. The poor outcome was only applicable to OS, not relapse-free survival (RFS); thus, CXCR4+ may be associated with a poor prognosis after recurrence. Intensive therapy, including administration of CXCR4 antagonists, may be promising for pediatric AML patients with LR.
authors.affiliation: Department of Human Health Sciences, Kyoto University, Kyoto, Japan.|Department of Clinical Laboratory, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Matsuo
authors.affiliation: Department of Human Health Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Nakamura
authors.affiliation: Division of Leukemia and Lymphoma, Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tomizawa
authors.affiliation: Clinical Research Center, National Nagoya Hospital, Aichi, Japan.
authors.forename: Akiko Moriya
authors.initials: AM
authors.lastname: Saito
authors.affiliation: Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Kiyokawa
authors.affiliation: Clinical Research Center, National Nagoya Hospital, Aichi, Japan.
authors.forename: Keizo
authors.initials: K
authors.lastname: Horibe
authors.affiliation: Department of Human Health Sciences, Kyoto University, Kyoto, Japan.|Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nishinaka-Arai
authors.affiliation: Department of Pediatrics, Kyoto University, Kyoto, Japan.
authors.forename: Mayu
authors.initials: M
authors.lastname: Tokumasu
authors.affiliation: Department of Human Health Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
authors.affiliation: Department of Human Health Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kamikubo
authors.affiliation: Department of Pediatrics, National Hospital Organization, Fukuoka-Higashi Medical Center, Fukuoka, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakayama
authors.affiliation: Department of Pediatrics, St. Marianna University School of Medicine, Kanagawa, Japan.
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Kinoshita
authors.affiliation: Department of Pediatrics, Shiga University of Medical Science, Shiga, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Taga
authors.affiliation: Department of Pediatrics, Osaka National Hospital, Osaka, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Tawa
authors.affiliation: Department of Molecular Diagnostics and Therapeutics, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Taki
authors.affiliation: Department of Pharmacoepidemiology, Kyoto University, Kyoto, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Department of Human Health Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Souichi
authors.initials: S
authors.lastname: Adachi
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D007564:Japan; D015470:Leukemia, Myeloid, Acute / Q000401:mortality* / Q000473:pathology*; D008297:Male; D009154:Mutation; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D012189:Retrospective Studies; D013163:Splenomegaly / Q000473:pathology; D016019:Survival Analysis
chemical_list: C527276:CXCR4 protein, human; D019718:Receptors, CXCR4; D019009:Proto-Oncogene Proteins c-kit
keywords: CXCR4; KIT; pediatric acute myeloid leukemia; prognostic factor, t(8;21)