JWA, a novel signaling molecule, involved in the induction of differentiation of human myeloid leukemia cells

Biochem Biophys Res Commun. 2006 Mar 10;341(2):440-50. doi: 10.1016/j.bbrc.2005.12.197. Epub 2006 Jan 11.


Dysregulation of hematopoietic cellular differentiation contributes to leukemogenesis. Unfortunately, relatively little is known about how cell differentiation is regulated. JWA (AF070523) is a novel all-trans retinoic acid (ATRA) responsible gene that initially isolated from ATRA-treated primary human tracheal bronchial epithelial cells. For the notable performance achieved by ATRA in the differentiation induction therapy, we investigated the role of JWA in the induction of differentiation of human myeloid leukemia cells. Our results showed that JWA was not only regulated by ATRA but also by several other differentiation inducers such as phorbol-12-myristate-13-acetate (TPA), arabinoside (Ara-C), and hemin, involved in the mechanisms of differentiation along different lineages of myeloid leukemia cells arrested at different stages of development. Generally, JWA was up-regulated by these inducers in a time-dependent manner. Inhibition of JWA by RNA interference decreased the induced cellular differentiation. However, in NB4 cells treated with ATRA, dissimilar with others, the expression of JWA was down-regulated, and the induced cellular differentiation could be enhanced by silencing of JWA. Collectively, JWA works as a potential critical molecule, associated with multi-directional differentiation of human myeloid leukemia cells. In NB4 cells, JWA may function as a lineage-restricted gene during differentiation along the monocyte/macrophage-like or granulocytic pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Bone Marrow Cells / metabolism
  • Cell Cycle
  • Cell Differentiation
  • Cell Line, Tumor
  • Cells, Cultured
  • Cytarabine / pharmacology
  • Gene Silencing
  • Granulocytes / metabolism
  • HL-60 Cells
  • Heat-Shock Proteins / metabolism
  • Heat-Shock Proteins / physiology*
  • Hemin / chemistry
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • K562 Cells
  • Leukemia, Myeloid / metabolism*
  • Macrophages / metabolism
  • Membrane Transport Proteins
  • Monocytes / metabolism
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tetradecanoylphorbol Acetate / pharmacology
  • Time Factors
  • Tretinoin / metabolism*
  • U937 Cells


  • ARL6IP5 protein, human
  • Heat-Shock Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Transport Proteins
  • Cytarabine
  • Tretinoin
  • Hemin
  • Tetradecanoylphorbol Acetate