Blood. 2003 Nov 15;102(10):3514-20. Epub
2003 Jul 31.
Comment in: Blood. 2004 May
15;103(10):3989-90; author reply 3990-1.
Transient
down-modulation of CD20 by rituximab in patients with chronic lymphocytic leukemia.
Jilani
I, O'Brien
S, Manshuri
T, Thomas
DA, Thomazy
VA, Imam
M, Naeem
S, Verstovsek
S, Kantarjian
H, Giles
F, Keating
M, Albitar
M. Department
of Hematopathology,
Lymphoid cells in most patients with chronic lymphocytic leukemia (CLL), when treated with
rituximab, become CD20-. This is thought to be due to masking of CD20 by rituximab. We
used specific antimouse immunoglobulin antibodies to detect rituximab on the surface of
CLL lymphocytes and we demonstrate that rituximab is rarely detectable after therapy. Only
3 of 65 patients with CLL had rituximab detectable on their lymphocytes after rituximab
therapy despite the fact that most had no detectable CD20 expression. In vitro mixing of
CLL or Raji cells with rituximab demonstrated that rituximab was detectable on the surface
of cells due to its binding to CD20. However, the addition of plasma led to the
down-modulation of CD20 expression, and the rituximab became undetectable. This
down-modulation of CD20 protein expression was associated with a down-modulation of CD20
mRNA. CLL cells that lost their CD20 expression regained CD20 expression after 24 hours in
culture. These data suggest that rituximab therapy leads to a substantial but transient
down-modulation of CD20 expression and that negativity for CD20 in cells from patients
treated with rituximab is not necessarily due to CD20 masking. The importance of this
down-modulation in the efficacy of current therapy with rituximab needs further
investigation.
PMID: 12893761 [PubMed - indexed for MEDLINE]