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Cited by 52Chronic Lymphocytic Leukemia ResearchLymphoma Diagnosis and TreatmentT-cell and Retrovirus Studies

Involvement of RhoH GTPase in the development of B-cell chronic lymphocytic leukemia

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Sanchez-Aguilera, A, Rattmann, I, Drew, D Z, Müller, L U W, Summey, V, Lucas, D M, Byrd, J C, Croce, C M +5 more·2010·Leukemia
DOI 10.1038/leu.2009.217PMC PMC3869226
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Abstract

RhoH is a hematopoietic-specific, GTPase-deficient member of the Rho GTPase family that functions as a regulator of thymocyte development and T-cell receptor signaling by facilitating localization of zeta-chain-associated protein kinase 70 (ZAP70) to the immunological synapse. Here we investigated the function of RhoH in the B-cell lineage. B-cell receptor (BCR) signaling was intact in Rhoh(-/-) mice. Because RhoH interacts with ZAP70, which is a prognostic factor in B-cell chronic lymphocytic leukemia (CLL), we analyzed the mRNA levels of RhoH in primary human CLL cells and showed a 2.3-fold higher RhoH expression compared with normal B cells. RhoH expression in CLL positively correlated with the protein levels of ZAP70. Deletion of Rhoh in a murine model of CLL (Emu-TCL1(Tg) mice) significantly delayed the accumulation of CD5(+)IgM(+) leukemic cells in peripheral blood and the leukemic burden in the peritoneal cavity, bone marrow and spleen of Rhoh(-/-) mice compared with their Rhoh(+/+) counterparts. Phosphorylation of AKT and ERK in response to BCR stimulation was notably decreased in Emu-TCL1(Tg);Rhoh(-/-) splenocytes. These data suggest that RhoH has a function in the progression of CLL in a murine model and show RhoH expression is altered in human primary CLL samples.

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Authors
Sanchez-Aguilera, A., Rattmann, I., Drew, D. Z., Müller, L. U. W., Summey, V, Lucas, D. M., Byrd, J. C., Croce, C. M., Gu, Y., Cancelas, J. A., Johnston, P., Moritz, T., & Williams, D. A.
Affiliations
  • Cincinnati Children's Hospital Medical Center (US)
  • The Ohio State University (US)
  • Boston Children's Hospital (US)
Corresponding author
Williams, D A
ORCID
Venue
Leukemia
Publisher
Springer Science and Business Media LLC
Published
2009-10-22
Volume
24
Issue
1
Pages
97-104
ISSN
  • 0887-6924 (ISSN-L)
  • 1476-5551
DOI
10.1038/leu.2009.217
PMC
PMC3869226
OpenAlex
W1984717527
Cited by
52
References
1
Citations by year
2026: 2 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 5 · 2013: 7 · 2012: 5
FWCI
2.11
Type
journal article
Language
en
Open access
Licence
Locations
  • Leukemia (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Cancer Institute (CA 113969, R01CA113969)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK062757)
Topics
  • Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
Keywords
RhoH, chronic lymphocytic leukemia, ZAP-70, B cell receptor signaling, Rho GTPases, Akt phosphorylation, ERK1/2 phosphorylation, leukemia progression
MeSH terms
Animals, Disease Models, Animal, Humans, Mice, Inbred C57BL, Phosphorylation, Receptors, Antigen, B-Cell, Transcription Factors, Leukemia, Lymphocytic, Chronic, B-Cell, rho GTP-Binding Proteins, Extracellular Signal-Regulated MAP Kinases, Proto-Oncogene Proteins c-akt, Mice, ZAP-70 Protein-Tyrosine Kinase

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