Receptor for hyaluronan acid-mediated motility (RHAMM) is a new immunogenic leukemia-associated antigen in acute and chronic myeloid leukemia.
OBJECTIVE
Identification of leukemia-associated antigens (LAA) eliciting an immune response in patients is a prerequisite for specific immunotherapy of leukemias. To identify new LAA, we used the method of serologic screening of cDNA expression libraries (SEREX).


METHODS
A SEREX library of the cell line K562 was subjected to allogeneic screening with sera from patients with acute myeloid leukemia (AML) or chronic myeloid leukemia (CML) vs sera from healthy volunteers.


RESULTS
The receptor for hyaluronan acid-mediated motility (RHAMM) involved in cell growth and metastasis was identified as a new LAA. Serologic responses to RHAMM were observed in patients with AML (42%), CML (31%), melanoma (83%), renal cell carcinoma (40%), breast cancer (67%), and ovarian carcinoma (50%), but not in HV or patients with autoimmune diseases. RHAMM mRNA was detectable in peripheral blood mononuclear cells (PBMN) of 60% of newly diagnosed AML patients. Western blotting stained positive for RHAMM protein in 70% of AML patients. mRNA expression of RHAMM also was found in patients with CML (40%), renal cell carcinoma (73%), breast carcinoma (60%), and ovarian carcinoma (50%). In melanoma, RHAMM mRNA expression was detected in metastases (80%) but not in primary tumors. RHAMM is differentially expressed: significant mRNA expression was not found in normal tissues, except from testis, placenta, and thymus, or in PBMN- and CD34-separated cell samples of healthy volunteers.


CONCLUSIONS
RHAMM is an immunogenic antigen in leukemias and solid tumors and might be a potential target structure for cellular immunotherapies and antibody therapies.
Greiner
Jochen
J
Third Department of Internal Medicine, University of Ulm, Ulm, Germany.
Ringhoffer
Mark
M
Taniguchi
Masanori
M
Schmitt
Anita
A
Kirchner
Dieter
D
Krähn
Gertraud
G
Heilmann
Volker
V
Gschwend
Jürgen
J
Bergmann
Lothar
L
Döhner
Hartmut
H
Schmitt
Michael
M
D000208:Acute Disease; D000912:Antibodies, Neoplasm / Q000276:immunology; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D001943:Breast Neoplasms / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism; D003199:Computer Systems; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D020014:K562 Cells / Q000378:metabolism; D007680:Kidney Neoplasms / Q000378:metabolism; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000378:metabolism; D007951:Leukemia, Myeloid / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D009000:Monocytes / Q000378:metabolism; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D009369:Neoplasms / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism; D009928:Organ Specificity; D010051:Ovarian Neoplasms / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C098946:hyaluronan-mediated motility receptor