Expression of IAP family proteins in myelodysplastic syndromes transforming to overt leukemia.
Bone marrow cells of patients with myelodysplastic syndromes (MDS) frequently undergo apoptosis, though the apoptotic cell ratio decreases when overt leukemia (OL) develops. Thus, we compared the expression of the inhibitor of apoptosis protein (IAP) gene family proteins in bone marrow samples from control, MDS, OL transformed from MDS (MDS --> OL), and de novo acute myelogenous leukemia (AML) subjects by the quantitative real-time RT-PCR method and an immunohistochemical approach. Overexpression of mRNA for survivin, cIAP1, NAIP and XIAP was significant in MDS bone marrow cells compared with control samples. However, the expression of mRNA for survivin, cIAP1 and cIAP2 exhibited a remarkable decrease after the development of OL (MDS --> OL). By immunohistochemistry, survivin was found to localize to the nucleus of myeloid cells in the majority of MDS cases. Next, the chronological changes in the expression of IAPs were determined in cases of MDS with evolution of OL. Although the expression of cIAP1 and cIAP2 revealed a sudden or gradual decrease as OL developed, survivin in many cases and XIAP in the majority of cases exhibited a peak of expression before a decline, indicating that these IAPs could be associated with the early events in the development of OL.
Yamamoto
Kouhei
K
Department of Pathology and Immunology, Aging and Developmental Sciences, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, 113-8519, Japan.
Abe
Shinya
S
Nakagawa
Yasunori
Y
Suzuki
Kenshi
K
Hasegawa
Maki
M
Inoue
Miori
M
Kurata
Morito
M
Hirokawa
Katsuiku
K
Kitagawa
Masanobu
M
D017209:Apoptosis; D001483:Base Sequence; D002455:Cell Division; D017931:DNA Primers; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D007938:Leukemia / Q000378:metabolism* / Q000473:pathology; D009190:Myelodysplastic Syndromes / Q000378:metabolism* / Q000473:pathology; D011506:Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044767:Ubiquitin-Protein Ligases
D017931:DNA Primers; D051034:Inhibitor of Apoptosis Proteins; D011506:Proteins; C494833:BIRC2 protein, human; D044767:Ubiquitin-Protein Ligases