Israel Medical Association Journal

The cause of death for Pharaoh Tutankhamun (ca. 1330–1324 BCE) is still unknown despite the advancement in modern paleopathology and the introduction of computed tomography mummy examination and modern molecular pathology, including PCR-based gene analysis. Many speculations regarding his unexpected death have been published, including crush injury, infectious diseases such as malaria, and hereditary disease. We discuss for the first time all these events that could have ultimately caused Tutankhamun's sudden death, particularly sickle cell disease, which can cause osteonecrosis and lead to walking disability, bone deformities, and fragility. Malaria-associated tropical splenomegaly, as an acquired infectious disease, and the crush injury, which represents an acute event, were verified by a left distal femur fracture that contributed to splenic rupture as a major fatal event. We highlight important issues that can provide clinicians and clinical care practitioners with a broad vision while analyzing such cases.

Background: The highly tissue-specific trafficking of normal and malignant lymphocytes to particular organs is mediated by adhesion molecules, or “homing receptors.” Among our patients with B cell chronic lymphocytic leukemia 15% demonstrate predominantly splenic manifestations and are classified as stage II(S).

Objective: To investigate whether expression of cell surface adhesion molecules can distinguish stage II(S) patients from stage 0 or stage 0 and I CLL[1] patients.

Methods: Expression of adhesion molecules belonging to different families was studied in CD19-positive cells isolated from the blood of 42 patients by dual color flow cytometry. The families included: immunoglobulin superfamily (CD54, CD58), integrin family (β1, β2 and β3 chains, CD11a, CD11c CD49d), selectin family (L-selectin), and lymphocyte homing receptor family (CD44).

Results: The average percentage of leukemic cells expressing CD11c in the 23 patients with stage II(S) was 25.7 compared with 13.2% in the 14 patients with stage 0 disease (P = 0.047). The average percentage of leukemic cells expressing CD44 in patients with stage II(S) was 90.5 compared with 77.2% in patients with stage 0 (P = 0.007) and 80% in patients with stages 0 and I together (n=19, P = 0.008). Other adhesion molecules tested did not show a statistically significance difference in expression between the different disease stages.

Conclusions: The higher expression of CD44 and CD11c in cells of CLL patients with predominantly splenic manifestations may account for the tendency of their lymphocytes to home to the spleen.