Constitutively activated Rho guanosine triphosphatases regulate the growth and morphology of hairy cell leukemia cells.
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-Racl 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.
Department of Hematology/Oncology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Xian
X
Zhang
Takashi
T
Machii
Itaru
I
Matsumura
Sachiko
S
Ezoe
Akira
A
Kawasaki
Hirokazu
H
Tanaka
Shuji
S
Ueda
Hiroyuki
H
Sugahara
Hirohiko
H
Shibayama
Masao
M
Mizuki
Yuzuru
Y
Kanakura
D000199:Actins; D001399:Azure Stains; D002455:Cell Division; D048429:Cell Size; D006801:Humans; D007943:Leukemia, Hairy Cell / Q000473:pathology*; D010641:Phenotype; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism / Q000502:physiology; D020830:rac1 GTP-Binding Protein / Q000378:metabolism / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000378:metabolism* / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism / Q000502:physiology
D000199:Actins; D001399:Azure Stains; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein