Expression dynamics of drug resistance genes, multidrug resistance 1 (MDR1) and lung resistance protein (LRP) during the evolution of overt leukemia in myelodysplastic syndromes.

Abstract

It is well-known that leukemic cells of overt leukemia (OL) that have transformed from myelodysplastic syndromes (MDS) are more resistant to chemotherapy as compared with de novo AML cells. Thus, to examine the expression levels of drug-resistant genes and their alterations with the development of OL in MDS, the expression of mRNA for MDR1 and LRP was determined in bone marrow samples from control, de novo AML, MDS, MDS at the time of OL transformation (MDS --> OL), and after transformation (OL) by quantitative real-time RT-PCR. The expression of MDR1 in MDS bone marrow at the time of initial diagnosis was as low as that for control subjects. However, the expression level was significantly elevated at the time of the development of OL (MDS --> OL) compared with the initial MDS subjects (P < 0.05), while expression was relatively reduced after OL development (OL). The expression of LRP was significantly higher in MDS and MDS --> OL samples than control subjects. However, the high expression of LRP in MDS --> OL was significantly reduced after OL development (OL). The expression levels of drug-resistant genes in MDS --> OL or OL were not significantly higher than those of de novo AML samples, although LRP expression in MDS or MDS --> OL was relatively higher than that of de novo AML. Detecting increases in the expression of MDR1 would be useful for predicting OL development in MDS patients.

• Authors: Morito Kurata, Maki Hasegawa, Yasunori Nakagawa, Shinya Abe, Kouhei Yamamoto, Kenshi Suzuki, Masanobu Kitagawa
• Journal: Experimental and molecular pathology (Exp Mol Pathol) Vol. 81 Issue 3 Pg. 249-54 (Dec 2006) ISSN: 0014-4800 [Print] Netherlands
• PMID: 16566920 (Publication Type: Journal Article)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• RNA, Messenger
• Vault Ribonucleoprotein Particles
• major vault protein

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (genetics)
• Adult
• Aged
• Biological Evolution
• Case-Control Studies
• Disease Progression
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Leukemia (genetics)
• Male
• Middle Aged
• Myelodysplastic Syndromes (genetics)
• RNA, Messenger (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Vault Ribonucleoprotein Particles (genetics)