title: Elevated levels of transferrin receptor 2 mRNA, not transferrin receptor 1 mRNA, are associated with increased survival in acute myeloid leukaemia.
abstract: Transferrin receptor 1 (TfR1) is a type II membrane protein that mediates cellular iron uptake. Transferrin receptor 2(TfR2), another receptor for transferrin (Tf), has recently been cloned. We examined expression levels of TfR1, TfR2-alpha (membrane form) and TfR2-beta (non-membrane form) transcripts in cells from 67 patients with de novo acute myeloid leukaemia (AML) using reverse transcription-polymerase chain reaction (RT-PCR), and correlated the results with a variety of clinical features and disease outcomes of these patients. Significant correlations were noted between the levels of both TfR1 and TfR2-alpha (r = 0.771, P < 0.001) and TfR1 and TfR2-beta (r = 0.534, P < 0.001). Unexpectedly, initial white blood cell (WBC) counts were inversely correlated with levels of expression of either TfR1(r = -0.357, P = 0.003), TfR2-alpha (r = -0.486, P < 0.0001), or TfR2-beta (r = -0.435, P = 0.0003). Only TfR2 expression was significantly associated with either serum iron (r = -0.270, P = 0.045) or serum ferritin (r = -0.364, P = 0.008). Multivariate analyses using Cox's proportional hazard model showed that elevated TfR2-alpha, but not TfR1 or TfR2-beta mRNA levels significantly contributed to a better prognosis for AML patients. Furthermore, a group with high expression levels of both TfR2-alpha and TfR2-beta survived significantly longer than a group without high expression of both of them (P < 0.01 by log-rank). The present study suggests that (i) TfRs-independent iron uptake might have an important role in in vivo proliferation of AML cells; (ii) expression of TfR2 (especially the alpha form) is a novel prognostic factor for patients with AML.
authors.affiliation: Department of Haematology, Showa University School of Medicine, Tokyo, Japan. nakamaki@med.showa-u.ac.jp
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Nakamaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawabata
authors.forename: Bungo
authors.initials: B
authors.lastname: Saito
authors.forename: Manabu
authors.initials: M
authors.lastname: Matsunawa
authors.forename: Junko
authors.initials: J
authors.lastname: Suzuki
authors.forename: Daisuke
authors.initials: D
authors.lastname: Adachi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tomoyasu
authors.forename: H
authors.initials: H
authors.lastname: Phillip Koeffler
mesh_terms: D000208:Acute Disease; D000368:Aged; D015703:Antigens, CD; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005293:Ferritins / Q000097:blood; D015870:Gene Expression; D006801:Humans; D007501:Iron / Q000097:blood; D007951:Leukemia, Myeloid / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D011990:Receptors, Transferrin / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C068126:CD71 antigen; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011990:Receptors, Transferrin; C503640:TFR2 protein, human; D005293:Ferritins; D007501:Iron