title: [Analysis of molecular mechanism involved in development of acute myeloid leukemia].
abstract: We examined the role of molecules related to drug resistance, such as P-glycoprotein (P-gp) and telomerase (TERT), signaling molecules of STATs and FLT3 in leukemia pathogenesis in de novo acute myeloid leukemia (AML), and myelodysplastic syndrome in the phase of overt leukemia (MDS-OL). Subjects were 18 patients with de novo AML, in which expression of P-gp, TERT, STAT3, STAT5, and FLT3 was observed in 11, 14, 16, 18, and 14 of patients, respectively. Phosphorylation of STAT3, STAT5, and FLT3 in patients with de novo AML was observed in 10 out of 14, 14 out of 18, and 10 out of 14 patients, respectively. Phosphorylation of STAT5 was associated with expression of both P-gp and TERT, suggesting that STAT5 is one of the transcription factors for these genes. On the other hand, P-gp, TERT, STAT3, STAT5, and FLT3 were expressed in 3, 1, 1, 6, and 1 of the 7 patients with MDS-OL, respectively. While phosphorylation of STAT5 was observed in 4 out of 7 patients, phosphorylation of STAT3 or FLT3 was not detected in all cases examined. Telomere length varied from 2.7 kb to 6.0 kb in de novo AML, accompanied by an increased level of telomerase activity in 4 of 5 patients with de novo AML. In contrast, all MDS-OL cases showed a similar telomere length of 4-5 kb. These results indicate that consideration should be given to the differences of molecular mechanisms in the pathogenesis of de novo AML and MDS-OL for the treatment strategy of AML.
authors.affiliation: Dept of Pharmacy, Tokyo Women's Medical University Hospital.
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Katsumi
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Kawauchi
authors.forename: Koji
authors.initials: K
authors.lastname: Ozaki
authors.forename: Satoru
authors.initials: S
authors.lastname: Shimizu
authors.forename: Toshimi
authors.initials: T
authors.lastname: Kimura
authors.forename: Toshiko
authors.initials: T
authors.lastname: Motoji
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamada
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015139:Blotting, Southern; D015153:Blotting, Western; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D050791:STAT Transcription Factors / Q000378:metabolism; D019098:Telomerase / Q000502:physiology; D016615:Telomere
chemical_list: D050791:STAT Transcription Factors; D019098:Telomerase