title: The significance of low PU.1 expression in patients with acute promyelocytic leukemia.
abstract: BACKGROUND
  Although the importance of the hematopoietic transcription factor PU.1 in acute myeloid leukemia (AML) has been demonstrated, the expression of PU.1 in acute promyelocytic leukemia (APL) patient samples awaits further investigation. The current study used APL patient samples to assess the expression pattern of PU.1 in the initiation and progression of APL.
  
  
  RESULTS
  We used real-time RT-PCR to compare PU.1 expression between de novo APL patient samples and normal blood specimens, and the results indicated that PU.1 expression was significantly lower in newly diagnosed APL patient samples as compared to normal hematopoietic cells. Further evidence showed a significant inverse correlation between the expression level of PML-RARα and that of PU.1. In addition, we analyzed the correlation between PML-RARα and PU.1 expression in a large population of AML patients retrieved from the expression profiles. The results showed that PU.1 expression was lower in patients with APL than other AML subtypes and there was also a trend towards increasing PU.1 expression from AML-M0 to AML-M5, with the exception of AML-M3 (APL). These observations suggested that PU.1 expression was reduced by PML-RARα in APL patients. Furthermore, we measured PU.1 expression in APL-initiating cells isolated from de novo APL patients by side population cell analysis and found that suppression of PU.1 expression occurred concurrently with PML-RARα expression, indicating the pivotal role of PU.1 in APL initiation.
  
  
  CONCLUSIONS
  Our findings provide evidence that low PU.1 expression in APL patients is required for disease initiation and progression.
authors.affiliation: State Key Laboratory of Medical Genomics, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (CAS) & Shanghai Jiao Tong University School of Medicine (SJTUSM), Rui-Jin Hospital, SJTUSM, Shanghai, China.
authors.forename: Xuehua
authors.initials: X
authors.lastname: Zhu
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Maoxiang
authors.initials: M
authors.lastname: Qian
authors.forename: Xujie
authors.initials: X
authors.lastname: Zhao
authors.forename: Wentao
authors.initials: W
authors.lastname: Yang
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Ji
authors.initials: J
authors.lastname: Zhang
authors.forename: Kankan
authors.initials: K
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein