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

ABSTRACT

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.