Development-dependent expression of cyclin D3 in precursor T-cell lymphoblastic leukemia/lymphoma

In contrast to the clear oncogenic role of cyclins D1 and D2, cyclin D3 is suggested to have a role in the initiation and/or maintenance of differentiation in a lineage‐associated manner in addition to its basic role in proliferation. Recently, it has been reported that in cyclin D3‐deficient mice, normal expansion of T lymphocytes is impaired because of maturation arrest at the double‐negative thymocyte stage, suggesting a crucial role for cyclin D3 in early T‐cell development. Therefore, cyclin D3 expression was examined in 36 human precursor T‐lymphoblastic leukemia/lymphomas (T‐LBLL), a neoplastic counterpart of T cells at the early developmental stages of differentiation. Using a standard panel of differentiation markers, all T‐LBLL were categorized into four stages according to differentiation: progenitor, double‐negative, double‐positive, and single‐positive stages. Cyclin D3 expression was initiated at the boundary between double‐negative and double‐positive stages, and was sustained in the single‐positive stage. T‐cell receptor was expressed simultaneously with cyclin D3, whereas CD79a expression was specific in the double‐negative stage, and thus it was inversely correlated with that of cyclin D3. Taken together with the crucial and non‐redundant role in T‐cell development in mice, this molecule is suggested to play an important role in human T‐cell development.