Deregulation of calcium fluxes in HTLV-I infected CD4-positive T-cells plays a major role in malignant transformation.
The CD4+ T-cell malignancy induced by human T-cell leukemia virus type 1 (HTLV-I) infection and termed; Adult T-cell Leukemia lymphoma (ATLL), is caused by defects in the mechanisms underlying cell proliferation and cell death. In the CD4+ T-cells, calcium ions are central for both phenomena. ATLL is associated with a marked hypercalcemia in many patients. The consequence of a defect in the Ca2+ signaling pathway for lymphocyte activation is characterized by an impaired NFAT activation and transcription of cytokines, chemokines and many other NFAT target genes whose transcription is essential for productive immune defense. Fresh ATLL cells lack the TCR/CD3 and CD7 molecules on their surface. Whereas CD7 is a calcium transporter, reduction in calcium influx in response to T-cell activation was reported as a functional consequence of TCR/CD3 expression deficiency. Understanding these changes and identifying the molecular players involved might provide further insights on how to improve ATLL treatment.
Akl
Haidar
H
Experimental Hematology, Universite Libre de Bruxelles, Institut Jules Bordet 127 Boulevard de Waterloo, 1000 Bruxelles, Belgium. haidar.akl@ulb.ac.be
Badran
Bassam
B
El Zein
Nabil
N
Dobirta
Gratiela
G
Burny
Arsene
A
Martiat
Philippe
P
D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000821:virology*; D002118:Calcium / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism
D011948:Receptors, Antigen, T-Cell; D054334:Viral Regulatory and Accessory Proteins; C084305:p12I protein, Human T-lymphotropic virus 1; D002118:Calcium