Characterization of stage progression in chronic myeloid leukemia by DNA microarray with purified hematopoietic stem cells.
Chronic myeloid leukemia (CML) is characterized by the clonal expansion of hematopoietic stem cells (HSCs). Without effective treatment, individuals in the indolent, chronic phase (CP) of CML undergo blast crisis (BC), the prognosis for which is poor. It is therefore important to clarify the mechanism underlying stage progression in CML. DNA microarray is a versatile tool for such a purpose. However, simple comparison of bone marrow mononuclear cells from individuals at different disease stages is likely to result in the identification of pseudo-positive genes whose change in expression only reflects the different proportions of leukemic blasts in bone marrow. We have therefore compared with DNA microarray the expression profiles of 3456 genes in the purified HSC-like fractions that had been isolated from 13 CML patients and healthy volunteers. Interestingly, expression of the gene for PIASy, a potential inhibitor of STAT (signal transducer and activator of transcription) proteins, was down-regulated in association with stage progression in CML. Furthermore, forced expression of PIASy has induced apoptosis in a CML cell line. These data suggest that microarray analysis with background-matched samples is an efficient approach to identify molecular events underlying the stage progression in CML.
Ohmine
K
K
Division of Functional Genomics, Jichi Medical School, Kawachi-gun, Tochigi 329-0498, Japan.
Ota
J
J
Ueda
M
M
Ueno
S
S
Yoshida
K
K
Yamashita
Y
Y
Kirito
K
K
Imagawa
S
S
Nakamura
Y
Y
Saito
K
K
Akutsu
M
M
Mitani
K
K
Kano
Y
Y
Komatsu
N
N
Ozawa
K
K
Mano
H
H
D000071916:AC133 Antigen; D015703:Antigens, CD; D017209:Apoptosis; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D018450:Disease Progression; D015536:Down-Regulation; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors; D006023:Glycoproteins / Q000032:analysis; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010455:Peptides / Q000032:analysis; D000075223:Poly-ADP-Ribose Binding Proteins; D011379:Prognosis; D050828:Protein Inhibitors of Activated STAT; D012334:RNA, Neoplasm / Q000032:analysis*; D012190:Retroviridae / Q000235:genetics; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000071916:AC133 Antigen; D015703:Antigens, CD; D002352:Carrier Proteins; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; C485891:PIAS4 protein, human; D010455:Peptides; D000075223:Poly-ADP-Ribose Binding Proteins; D050828:Protein Inhibitors of Activated STAT; D012334:RNA, Neoplasm