CD52 is expressed on human mast cells and is a potential therapeutic target in Waldenstrom's Macroglobulinemia and mast cell disorders.
BACKGROUND
Alemtuzumab is a monoclonal antibody used in the treatment of CD52-expressing B-cell malignancies, including Waldenstrom's macroglobulinemia (WM). Recent studies demonstrate high levels of alemtuzumab activity in relapsed/refractory disease. One potential target of alemtuzumab is bone marrow mast cells (BMMCs), which provide growth and survival signaling for WM lymphoplasmacytic cells.


METHODS
We therefore examined BMMCs (FceRI+, CD117+) from WM and other mast cell (MC) disorders for expression of CD52.


RESULTS
We identified cell surface antigen expression by multicolor flow cytometric analysis and found CD52 expressed on human mast-derived cell line-1 (HMC-1) and LAD2 MC lines, on BMMC from 13 of 15 patients with WM, and on BMMCs from 4 of 4 patients with systemic mastocytosis (SM). None of 4 healthy donors expressed CD52. Reverse-transcriptase polymerase chain reaction analysis confirmed CD52 expression in the HMC-1 and LAD2 MC lines, in BMMCs from 14 of 15 patients with WM, and 3 of 3 patients with SM. CD52 transcripts were also detected in BMMCs from 6 of 6 healthy donors, despite the absence of CD52 cell surface expression. Importantly, we observed high levels of alemtuzumab-mediated, antibody-dependent, cell-mediated cytotoxicity against LAD2 MCs and BMMCs from patients with WM and SM.


CONCLUSIONS
These studies demonstrate that CD52 is widely expressed on human MCs and WM bone marrow lymphoplasmacytic cells and provide the preclinical rationale for the use of alemtuzumab in the treatment of WM and possibly other MC-related disorders.
Santos
Daniel Ditzel
DD
Bing Center for Waldenstrom's Macroglobulinemia, Dana-Farber Cancer Institute.
Hatjiharissi
Evdoxia
E
Tournilhac
Olivier
O
Chemaly
Mariana Z A
MZ
Leleu
Xavier
X
Xu
Lian
L
Patterson
Christopher
C
Branagan
Andrew R
AR
Manning
Robert J
RJ
Ho
Allen W
AW
Hunter
Zachary R
ZR
Dimmock
Elizabeth A
EA
Kutok
Jeffery L
JL
Churchill
Winthrop H
WH
Castells
Mariana C
MC
Tai
Yu-Tzu
YT
Anderson
Kenneth C
KC
Treon
Steven P
SP
D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000276:immunology* / Q000473:pathology; D000074301:CD52 Antigen; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008415:Mastocytosis / Q000188:drug therapy* / Q000276:immunology; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy* / Q000276:immunology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D000074323:Alemtuzumab