Overexpression of the Doppel protein in acute myeloid leukaemias and myelodysplastic syndromes.
We investigated the expression patterns and distribution of Doppel (Dpl), the product of the prion-like gene PRND, in the leukaemic cell lines HL-60 and K562 and in bone marrow cells from 44 patients with acute myeloid leukaemia (AML) and 63 patients with myelodysplastic syndrome (MDS). Whereas normal samples were negative or showed very weak expression that was restricted to CD34(+) cells, Dpl was detected in both cell lines and in most AML and MDS cases by immunocytochemistry and Western blotting. Quantitative reverse transcription polymerase chain reaction revealed variable mRNA levels in almost all AML and MDS cases, but barely detectable levels in normal bone marrow. These differences were confirmed by in situ hybridization. PRND expression was higher in advanced compared with early MDS (P = 0.01), but Dpl levels did not predict disease progression. In AML there was no correlation between Dpl levels and clinical or laboratory findings. In conclusion, this is the first time that the expression of PRND has been demonstrated in human bone marrow. The molecular mechanism of the observed overexpression is unknown; however, the differential Dpl distribution in AML and MDS versus healthy subjects makes it a possible leukaemia-associated antigen that could be useful for diagnostic and therapeutic purposes.
Travaglino
Erica
E
Internal Medicine and Medical Oncology, University of Pavia, IRCCS Poloclinico S. Matteo, 27100 Pavia, Italy.
Comincini
Sergio
S
Benatti
Chiara
C
Azzalin
Alberto
A
Nano
Rosanna
R
Rosti
Vittorio
V
Ferretti
Luca
L
Invernizzi
Rosangela
R
D000208:Acute Disease; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D015153:Blotting, Western; D005260:Female; D058851:GPI-Linked Proteins; D018922:HL-60 Cells; D006801:Humans; D007150:Immunohistochemistry; D007951:Leukemia, Myeloid / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000379:methods; D011328:Prions / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
D018952:Antigens, CD34; D058851:GPI-Linked Proteins; C501125:PRND protein, human; D011328:Prions; D012333:RNA, Messenger