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 i n the indolent, chronic phase (CP) of CML undergo blast crisis (BC), the pr ognosis for which is poor. It is therefore important to clarify the mechani sm underlying stage progression in CML. DNA microarray is a versatile tool for such a purpose. However, simple comparison of bone marrow mononuclear c ells from individuals at different disease stages is likely to result in th e identification of pseudo-positive genes whose change in expression only r eflects the different proportions of leukemic blasts in bone marrow. We hav e therefore compared with DNA microarray the expression profiles of 3456 ge nes in the purified HSC-like fractions that had been isolated from 13 CML p atients and healthy volunteers. Interestingly, expression of the gene for P IASy, a potential inhibitor of STAT (signal transducer and activator of tra nscription) proteins, was down-regulated in association with stage progress ion in CML. Furthermore, forced expression of PIASy has induced apoptosis i n a CML cell line. These data suggest that microarray analysis with backgro und-matched samples is an efficient approach to identify molecular events u nderlying the stage progression in CML.