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Soluble CD22 as a tumor marker for hairy cell leukemia
Kakushi Matsushita1, Inger Margulies, Masanori Onda
1Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20854-4255, USA.
Insights
Soluble CD22 (sCD22) is detected in hairy cell leukemia (HCL) patients' blood, correlating with disease burden. Elevated sCD22 levels in HCL patients normalize with treatment response and do not impede anti-CD22 therapies.
Area of Science:
- Immunology
- Hematology
- Oncology
Background:
- CD22 is a key target for B-cell malignancy immunotherapies.
- The soluble form of CD22 (sCD22) has not been previously reported in patient blood.
- Hairy cell leukemia (HCL) is a B-cell malignancy where CD22 is a significant target.
Purpose of the Study:
- To investigate the presence and clinical utility of soluble CD22 (sCD22) in the blood of HCL patients.
- To establish a method for quantifying sCD22 levels.
- To correlate sCD22 levels with disease characteristics and treatment response.
Main Methods:
- Immunoaffinity and enzyme-linked immunosorbent assay (ELISA) techniques were employed.
- Monoclonal antibodies targeting CD22 were used for detection.
- sCD22 levels were measured in serum from 93 HCL patients and 23 healthy donors.
Main Results:
- The 100-kDa extracellular domain of CD22 and an 80-kDa processed form (sCD22) were identified in HCL patient serum.
- Median sCD22 levels were significantly higher in HCL patients (18 ng/mL) compared to normal donors (0.6 ng/mL).
- sCD22 levels correlated with circulating HCL cell counts and spleen size, and normalized with complete treatment response.
Conclusions:
- Serum sCD22 is a novel biomarker in HCL, reflecting disease burden.
- sCD22 levels can be monitored to assess treatment response in HCL patients.
- sCD22 may offer a more specific marker than sCD25 in certain HCL patient subsets and does not interfere with BL22 immunotoxin efficacy.
Abstract:
CD22 is an important immunotherapeutic target on B-cell malignancies, particularly hairy cell leukemia (HCL), but its soluble extracellular domain, sCD22, has not yet been reported in the blood. By immunoaffinity and enzyme-linked immunosorbent assay techniques using anti-CD22 monoclonal antibodies, we identified the 100-kDa extracellular domain of CD22 and an 80-kDa processed form in serum of patients with HCL. The median sCD22 level measured by enzyme-linked immunosorbent assay was 18 ng/mL for 93 patients with HCL. sCD22 levels varied from 2.1 to 163 ng/mL and were higher (P < .001) than 23 normal donors (median, 0.6 ng/mL). More than 95% of normal donors had sCD22 levels less than 1.9 ng/mL. sCD22 levels were proportional to concentrations of circulating HCL cells (P = .002), and HCL spleen size (P < .001). sCD22 levels normalized with complete but not partial response to treatment. sCD22 levels up to 300 ng/mL had less than a 2-fold effect on the cytotoxicity of the anti-CD22 recombinant immunotoxin BL22. sCD22 levels may be useful to follow in patients with HCL and may be more specific than sCD25 in patients with CD22(+)/CD25(-) disease. Trials are listed on www.cancer.gov as NCT00002765, NCT00021983, NCT00074048, NCT00085085, NCT00337311, and NCT00462189.
