201. Expression profiling of [CD34.sup.+] hematopoietic stem/ progenitor cells reveals distinct subtypes of therapy-related acute myeloid leukemia
- Author
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Qian, Zhijian, Fernald, Anthony A., Godley, Lucy A., Larson, Richard A., and Le Beau, Michelle M.
- Subjects
Myelocytic leukemia -- Genetic aspects ,Myelocytic leukemia -- Research ,Myelocytic leukemia -- Physiological aspects ,Nonlymphoid leukemia ,Science and technology ,National Academy of Sciences -- Research - Abstract
One of the most serious consequences of cytotoxic cancer therapy is the devefopmentof therapy-related acute myeloid leukemia (t-AML), a neoplastic disorder arising from a multipotential hematopoietic stem cell. To gain insights into the molecular basis of this disease, we performed gene expression profiling of [CD34.sup.+] hematopoietic progenitor cells from t-AML patients. Our analysis revealed that there are distinct subtypes of t-AML that have a characteristic gene expression pattern. Common to each of the subgroups are gene expression patterns typical of arrested differentiation in early progenitor cells. Leukemias with a -5/del(5q) have a higher expression of genes involved in cell cycle control (CCNA2, CCNE2, CDC2), checkpoints (BUB1), or growth (MYC), and loss of expression of the gene encoding IFN consensus sequence-binding protein (ICSBP). A second subgroup of t-AML is characterized by down-regulation of transcription factors involved in early hematopoiesis (TAL1, GATA1, and EKLF) and overexpression of proteins involved in signaling pathways in myeloid cells (FLT3) and cell survival (BCL2). Establishing the molecular pathways involved in t-AML may facilitate the identification of selectively expressed genes that can be exploited for the development of urgently needed targeted therapies.
- Published
- 2002