Constitutively Activated Rho Guanosine Triphosphatases Regulate the Growth and Morphology of Hairy Cell Leukemia Cells

Abstract

Hairy cell leukemia (HCL) is a rare type of chronic B-cell leukemia characterized by the hairy morphology of the leukemia cells. All of 5 HCL samples and an HCL-derived cell line, BNBH-I, showed serrated edges and hairlike projections in May-Grünwald Giemsa stain and protruding actin spikes and lamellipodia in phalloidin stain.These structures were hardly detected on B-cell chronic lymphocytic leukemia (B-CLL) and precursor B-cell acute lymphocytic leukemia (B-ALL) cells. Because Rho guanosine triphosphatases (GTPases) regulate the formation of these structures, we examined the expression levels and activation states of Rho GTPases in HCL cells. RhoA, Rac1, and Cdc42 were overexpressed and constitutively activated in HCL samples and BNBH-I cells but not in B-CLL or precursor B-ALL cells. Next we overexpressed dominant-negative (DN)- RhoA, DN-Rac1, and DN-Cdc42 in BNBH-I.As a result, each DN mutant repressed the growth of BNBH-I cells by more than 50% and inhibited actin spike formation, but only DN-Rac1 suppressed lamellipodia formation.We also found that enforced expression of constitutively active-RhoA, Rac, or Cdc42 in the proB-cell line Ba/F3 was sufficient to induce actin spike formation, whereas none of these molecules produced lamellipodia. These results indicated that constitutively activated Rho GTPases regulate the growth and unique morphology of HCL cells.

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Correspondence to Xian Zhang or Takashi Machii or Itaru Matsumura or Sachiko Ezoe or Akira Kawasaki or Hirokazu Tanaka or Shuji Ueda or Hiroyuki Sugahara or Hirohiko Shibayama or Masao Mizuki or Yuzuru Kanakura.

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Zhang, X., Machii, T., Matsumura, I. et al. Constitutively Activated Rho Guanosine Triphosphatases Regulate the Growth and Morphology of Hairy Cell Leukemia Cells. Int J Hematol 77, 263–273 (2003). https://doi.org/10.1007/BF02983784

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Key words

  • Rho
  • Rac
  • Cdc42
  • Hairy cell leukemia