Immunophenotypic Evaluation of CD305 and CD85d in B-Cell Lymphoid Neoplasms

B-cell lymphoproliferative disorders (B LPDs) constitute a wide spectrum of clonal B-cell neoplasms, ranging from indolent chronic illness to more aggressive hematologic malignancies. Clinically, patients may present with lymphadenopathy, splenomegaly, cytopenias, or, in chronic cases, may be diagnosed accidentally by the presence of lymphocytosis during routine complete blood counts, confirmed by immunophenotyping showing a monoclonal B-cell population (1).

According to the World Health Organization Classification of Haematolymphoid Tumours, 5th edition (WHO HAEM5), mature B-cell neoplasms are diagnosed by integrating morphology, immunophenotyping, cytogenetics, and molecular features. Major B-CLPD subtypes include chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), hairy cell leukemia (HCL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), follicular lymphoma (FL), and lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) (2). Accurate immunophenotypic diagnosis is essential as it helps to identify distinct prognoses and therapeutic approaches.

B-cell acute lymphoblastic leukemia/lymphoma is the most common pediatric leukemia, representing about 85% of ALL cases in children and 75% in adults. B-cell acute lymphoblastic leukemia/lymphoma is a precursor B-lineage neoplasm comprising lymphoblasts that express CD19, CD22, CD79a, and/or PAX5, besides the expression of immaturity markers such as TdT and CD34, while lacking surface immunoglobulin expression (3-5). Its inclusion differentiates the spectrum of B-cell neoplasms from precursor to mature stages.

Management of asymptomatic patients with B-CLPDs commonly follows a "watch and wait" strategy, whereas B-ALL requires prompt therapeutic intervention. Prognostic indicators in B-CLPDs, such as genetic mutations detected by fluorescence in situ hybridization (FISH) (del(17p), del(11q), trisomy 12, del(13q)), IGHV gene somatic hypermutation status, and TP53 mutations, can guide risk stratification and predict time to first treatment (TTFT) (6).

Inhibitory immune receptors, including CD85d and CD305 (LAIR-1), act as immune checkpoint-like molecules. They contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that recruit SH2-domain phosphatases (e.g., SHP-1), which suppress cellular activation (7,8).

CD85d is predominantly expressed in myeloid cells, including monocytes, macrophages, dendritic cells, and granulocytes. It is also differentially expressed on NK, T, B cells, and neutrophils. It is expressed at high levels in tumor cells, facilitating immune escape by promoting immune suppression, allowing for tumor evasion (9).

CD85d is widely expressed across AML, so it is a top candidate, due to its traditional association with myeloid phenotypes and limited expression in normal haematopoiesis (10). It was reported to be expressed in B cells of CLL patients in contrast to normal B cells. Its expression in CLL patients denotes a distinctive feature, which may be acquired during malignant transformation (8). Therefore, CD85d may have significant prognostic, mechanistic, and therapeutic roles in hematologic malignancies (11).

As a novel biomarker in solid malignant tumors to predict the prognosis of patients, upregulation of CD85d in tumors is associated with worse tumor phenotypes. Targeting CD85d may be an effective tool for targeted cancer therapy (12).

Concerning CD305, it has been reported in about 60% of CLL patients and may be used as an effective prognostic marker to predict TTFT in CLL patients (13).

Despite their potential clinical significance, the expression patterns of CD85d and CD305 across B-cell lymphoid neoplasms subtypes remain incompletely identified. Illustrating their role may help to determine TTFT, prognosis, therapeutic targeting, and refinement of B-cell neoplasms classification in line with WHO-HAEM5 standards.

Inclusion criteria

• - Newly diagnosed cases of B-cell acute lymphoblastic leukemia/lymphoma or B CLPDs according to the WHO classification and established by morphology, immunophenotyping, and, if available, cytogenetic/molecular findings.

Exclusion criteria

• Patients diagnosed with hematologic malignancies other than B-cell acute lymphoblastic leukemia/lymphoma or B CLPDs.
• Patients who have received prior therapy, including chemotherapy or immunomodulatory treatment.
• Patients refused to sign informed consent.