Gene expression in CD34(+) cells from normal bone marrow and leukemic origins.

Abstract

To address the molecular regulation of hematopoiesis and the complex mechanism in leukemogenesis, we established the first catalogs of genes expressed in normal bone marrow and leukemia CD34(+) cells. CD34(+) cell cDNA libraries were constructed using mRNA from adult bone marrow and from a case of acute myeloid leukemia-M5 transformed from myelodysplastic syndrome (MDS-AML). Expressed sequence tags (ESTs) and full-length cDNAs were generated by sequencing and were annotated using bioinformatic tools. From a total of 4142 ESTs obtained from normal bone marrow, 3424 meaningful tags were integrated into 1630 clusters, representing 622 known genes, 522 dbEST entries and 486 novel sequences. Out of 5382 ESTs from MDS-AML, 1985 clusters were produced based on the analysis of 4321 useful ESTs, including 711 known genes, 657 known ESTs and 617 novel sequences. Among 251 transcripts found in both bone marrow and MDS-AML EST datasets and those present in only one dataset, 58 showed statistically significant differences in EST copy numbers between the two tissues (P<0.05). Twenty putative full-length cDNAs for novel genes were also cloned from the MDS-AML library. The distinct gene expression patterns in MDS-AML-CD34(+) cells as compared to normal control cells may contribute to the development and/or maintenance of the malignant phenotypes of leukemia cells.