Yuling Luo, PhD

Advanced Cell Diagnostics Inc (ACD), a global technology and market leader for in situ nucleic acid detection for life science research and clinical diagnostics, has been awarded a 2-year, $1.4 million Phase II grant from the National Cancer Institute (NCI) under its Small Business Innovation Research (SBIR) program.

ACD and its academic partner, the Cleveland Clinic, will use the grant to develop and validate a diagnostic test based on ACD’s proprietary RNAscope technology for discriminating various B-cell non-Hodgkin lymphomas (NHLs) from benign lymphoproliferative diseases.

“This award is a further validation of the clinical utility of RNAscope technology,” says Yuling Luo, PhD, president and CEO of ACD. “We are very pleased that NCI has recognized the diagnostic potential of RNAscope technology and are grateful for its continued support.”

Clonal expansion of B-lymphocytes harboring immunoglobulin (Ig) gene rearrangements is a hallmark of B-cell malignancy, and is commonly manifested as restricted expression of one of the two Ig light chain mRNAs and proteins (kappa and lambda). Clinical laboratory detection of Ig light chain restriction (LCR) is a helpful ancillary tool in the differential diagnosis that includes lymphoid hyperplasia, atypical lymphoid hyperplasia, chronic inflammation, and B-cell neoplasia.

LCR can be readily detected as an abnormal kappa/lambda surface immunoglobulin ratio by flow cytometry using fresh tissue—the current gold standard for LCR detection. In many clinical settings, however, formalin-fixed, paraffin-embedded (FFPE) tissue is often the only type of patient sample available for diagnostic evaluation. For the diagnosis of NHLs in such samples, detection of B-cell clonality by demonstrating the restricted expression of one of the two immunoglobulin light chains (kappa or lambda) would provide valuable molecular information.


Xiao-Jun Ma, PhD

However, there has been a long-standing technical challenge in detecting light chain mRNAs in FFPE tissues. Immunohistochemistry (IHC) and conventional chromogenic in situ hybridization (CISH) are feasible only for such B-cell neoplasms as plasma cell myeloma that express abundant kappa or lambda mRNA and protein, leaving the majority of B-cell lymphomas without a sensitive method of LCR detection.

RNAscope’s single-molecule sensitivity and single-cell resolution allow direct visualization of kappa and lambda mRNA in FFPE tissue section under a standard bright-field microscope, thus addressing an unmet diagnostic need in B-cell lymphoma that has existed for more than two decades.

“In Phase I, we developed a manual RNAscope-based assay for light chain mRNAs and demonstrated that it allowed determination of light chain restriction in virtually all types of NHL using FFPE, with 99% concordance with the current gold standard flow cytometry assay using fresh tissue,” says Xiao-Jun Ma, PhD, ACD’s chief scientific officer and principal investigator.


James Cook, MD, PhD

“This is an important advance in our ability to accurately diagnose B-cell lymphomas, because conventional IHC and CISH methods to establish clonality simply don’t work for the majority of NHLs for various reasons,” says James Cook, MD, PhD, hematopathologist and coinvestigator at the Cleveland Clinic.

The Phase II grant will develop a fully automated assay and advanced image analysis algorithms for objective interpretation to facilitate clinical adoption. For further information, visit Advanced Cell Diagnostics.