Orphan receptor tyrosine kinases ROR1 and ROR2 in hematological malignancies

Abstract

The receptor tyrosine kinase ROR1 has been shown to be overexpressed in chronic lymphocytic leukemia (CLL). The aim of this study was to further characterize the expression of ROR1 and the other member of the ROR family, ROR2, in other lymphoid and myeloid malignancies. Normal white blood cells and reactive lymph nodes were negative for ROR1 and ROR2. A significantly high and uniform surface expression of ROR1 was found in CLL/hairy cell leukemia (HCL) compared to mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), myelomas, acute lymphoblastic leukemia (ALL) and myeloid leukemias (p = 0.02 to < 0.001). The lowest proportion of ROR1+ cells was seen in FL, whereas CLL, HCL and CML had significantly higher numbers of ROR1+ cells. Longitudinal follow-up of individual patients with CLL revealed that ROR1+ cells remained stable over time in non-progressive patients, but increased when the disease progressed (p < 0.05). Thus, a variable staining pattern of ROR1 ranging from very high (CLL, HCL) and high (CML) to intermediate (myeloma and DLBCL) or low (FL) was noted. ROR2 was not detected in hematological malignancies.

Keywords::

• ROR1
• ROR2
• antibodies
• flow cytometry
• hematological malignancies

Potential conflict of interest

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This study was supported by grants from Vinnova, EUCAAD 200755, a project funded under the auspices of the EU Seventh Framework Programme, the CLL Global Research Foundation, the Cancer and Allergy Foundation, the Swedish Research Council, the Iranian Ministry of Health and Medical Education, the Swedish Cancer Society, the Cancer Society in Stockholm, the King Gustaf Vth Jubilee Fund, the Swedish Pediatric Cancer Foundation, the Karolinska Institute Foundations and the Stockholm County Council.