Characterization of stage progression in chronic myeloid leukemia by DNA microarray with purified hematopoietic stem cells

• Published in: Oncogene Vol. 20; no. 57; pp. 8249 - 8257
• Main Authors: OHMINE, Ken, OTA, Jun, AKUTSU, Miyuki, MITANI, Kinuko, KANO, Yasuhiko, KOMATSU, Norio, OZAWA, Keiya, MANO, Hiroyuki, UEDA, Masuzu, UENO, Shu-Ichi, YOSHIDA, Koji, YAMASHITA, Yoshihiro, KIRITO, Keita, IMAGAWA, Shigehiko, NAKAMURA, Yuichi, SAITO, Kenji
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 13.12.2001; Nature Publishing Group
• Subjects: AC133 Antigen; Antigens, CD; Apoptosis; Biological and medical sciences; Blast crisis; Bone marrow; Carrier Proteins - genetics; Carrier Proteins - physiology; Chronic myeloid leukemia; Deoxyribonucleic acid; Disease Progression; DNA; DNA microarrays; Down-Regulation; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic; Genetic Vectors; Glycoproteins - analysis; Hematopoietic stem cells; Hematopoietic Stem Cells - chemistry; Hematopoietic Stem Cells - metabolism; Humans; Intracellular Signaling Peptides and Proteins; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - diagnosis; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Leukocytes (mononuclear); Molecular and cellular biology; Myeloid leukemia; Neoplasm Staging; Oligonucleotide Array Sequence Analysis - methods; Peptides - analysis; Poly-ADP-Ribose Binding Proteins; Prognosis; Protein Inhibitors of Activated STAT; Retroviridae - genetics; RNA, Neoplasm - analysis; Stem cells; Transcription; Tumor Cells, Cultured; Up-Regulation; Human; Prognosis; Stem cell; Leukemia; DNA chip; Hematopoietic cell; Malignant hemopathy; Plant blast; Mechanism; Crisis; Characterization; Chronic; Treatment; Expansion
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1205029

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.