A combined hematological and molecular study of Hodgkin lymphoma in Palestine: insights into subtype-specific prognosis and the role of Claudin-6/GATA-4

Hodgkin Lymphoma (HL) is a heterogeneous malignant disorder in the human body's lymphatic system with distinct clinical and molecular features. The objective of this research was to assess the hematological and molecular status of HL patients in Palestine and explore potential prognostic indicators and potential targets requiring further evaluation. Certain hematological factors, i.e., anemia, increased levels of lactate dehydrogenase, and inflammatory markers, are included in the International Prognostic Score (IPS) for HL. This study highlights the clinical value of accessible hematological biomarkers in resource-limited healthcare settings. A retrospective cohort study was conducted on 557 HL lymph node biopsies (2017-2023) from Palestinian Health Information Center (PHIC) database and hospital medical records. Hematological parameters (hemoglobin, MCV) and biochemical markers (ESR, LDH) were analyzed. Claudin-6 (CLDN6) mRNA expression was quantified in lymph node tissues from HL patients (n = 25) and healthy donors (n = 25) via qRT-PCR, while protein levels were assessed by Western blot. Serum GATA-4 concentrations were measured by ELISA. Nodular Sclerosis was the most common form, which predominantly occurred in young patients with a relatively equal sex distribution. The highest frequency was found in Hebron. Hemoglobin levels differed between subtypes, with the lymphocyte-depleted subtype showing the lowest mean hemoglobin values; the Lymphocyte-Depleted (LD) subtype exhibited the lowest hemoglobin and MCV (74.77 fL), indicating microcytic anemia. ESR was elevated across subtypes, with the highest levels observed in the NOS (63.5 mm/h), reflecting aggressive disease. Male mortality was highest in Mixed Cellularity (87.5%) and NS (75%), while LD and Lymphocyte-Predominant subtypes showed no male deaths. Molecularly, CLDN6 mRNA and GATA-4 levels were significantly elevated in HL tissues (P < 0.001), though Claudin-6 protein expression remained unchanged, suggesting post-transcriptional regulation. This study represents the first combined hematological and molecular characterization of Hodgkin lymphoma in Palestine and provides preliminary evidence for CLDN6-GATA4 regulatory involvement in HL pathogenesis. The hematological changes in Palestinian HL patients are unique. The roles of CLDN6 and GATA-4 as potential markers remain preliminary and require further validation in the context of Hodgkin lymphoma.