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Elevated levels of transferrin receptor 2 mRNA, not transferrin receptor 1 mRNA, are associated with increased survival in acute myeloid leukaemia
Author(s) -
Nakamaki Tsuyoshi,
Kawabata Hiroshi,
Saito Bungo,
Matsunawa Manabu,
Suzuki Junko,
Adachi Daisuke,
Tomoyasu Shigeru,
Phillip Koeffler H.
Publication year - 2004
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2004.04866.x
Subject(s) - transferrin receptor , transferrin , receptor , myeloid , medicine , messenger rna , immunology , endocrinology , biology , gene , biochemistry
Summary 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‐α (membrane form) and TfR2‐β (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‐α ( r = 0·771, P < 0·001) and TfR1 and TfR2‐β ( 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‐α ( r = −0·486, P < 0·0001), or TfR2‐β ( 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‐α, but not TfR1 or TfR2‐β mRNA levels significantly contributed to a better prognosis for AML patients. Furthermore, a group with high expression levels of both TfR2‐α and TfR2‐β 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 α form) is a novel prognostic factor for patients with AML.