  Using DNA microarray and cluster analysis of expressed genes in a cloned line
(M1-t-p53) of myeloid leukemic cells, we have analyzed the expression of genes
that are preferentially expressed in different normal tissues. Clustering of
547 highly expressed genes in these leukemic cells showed 38 genes
preferentially expressed in normal hematopoietic tissues and 122 other genes
preferentially expressed in different normal non-hematopoietic tissues
including neuronal tissues, muscle, liver and testis. We have also analyzed the
genes whose expression in the leukemic cells changed after activation of
wild-type p53 and treatment with the cytokine interleukin 6 (IL-6) or the
calcium mobilizer thapsigargin (TG). Out of 620 such genes in the leukemic
cells that were differentially expressed in normal tissues, clustering showed
80 genes that were preferentially expressed in hematopoietic tissues and 132
genes in different normal non-hematopietic tissues that also included neuronal
tissues, muscle, liver and testis. Activation of p53 and treatment with IL-6 or
TG induced different changes in the genes preferentially expressed in these
normal tissues. These myeloid leukemic cells thus express genes that are
expressed in normal non-hematopoietic tissues, and various treatments can
reprogram these cells to induce other such non-hematopoietic genes. The results
indicate that these leukemic cells share with normal hematopoietic stem cells
the plasticity of differentiation to different cell types. It is suggested that
this reprogramming to induce in malignant cells genes that are expressed in
different normal tissues may be of clinical value in therapy.
