Naslov
Variations in ATM protein expression during normal lymphoid differentiation and among B-cell-derived neoplasias

Autori
Starczynski, Jane ; Simmons, William ; Flavell, Joanne ; Byrd, Phillip ; Stewart, Grant ; Kullar, Harjit ; Groom, Alix ; Crocker, John ; Moss, Paul ; Reynolds, Gary ; Glavina Durdov, Merica ; Taylor, Malcolm ; Fegan, Christopher ; Stanković, Tatjana ; Murray, Paul

Izvornik
American journal of pathology (0002-9440) 163 (2003), 2; 423-432

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
ATM protein; variations; lymphoid differentiation

Sažetak
The ataxia telangiectasia mutated (ATM) protein plays a central role in the cellular response to DNA double-strand breaks (DSBs). Developmentally programmed DSBs are restricted to cellular subsets within lymphoid tissues and we asked whether ATM expression is differentially regulated during lymphoid differentiation. We showed that immature B cells in bone marrow and immature T cells of the thymic cortex were negative or weakly ATM-positive. T cells of thymic medulla and peripheral tissues strongly expressed ATM. High levels of ATM were present in the B lymphocytes of the mantle zone and in plasma cells, while the majority of germinal center B cells were negative or weakly labeled. Therefore, ATM expression appears to be down-regulated at those stages of lymphoid development where physiological DNA DSBs occur. In B-chronic lymphocytic leukemia and mantle cell lymphoma we observed two categories: ATM-negative tumors, most likely reflecting the presence of ATM mutation, and tumors with abundant ATM expression. Most follicular center-cell lymphomas and diffuse large B-cell lymphomas, which rarely show inactivation of the ATM gene, were negative or weakly ATM-positive. Tumor cells from most cases of Hodgkin's disease were ATM-negative. Therefore, unless ATM inactivation occurs, ATM expression in lymphoid tumors is likely to reflect their cellular origin. As a result, immunostaining to identify lymphoid neoplasias with ATM inactivation might only be feasible for tumors derived from the stages where ATM is constitutively highly expressed.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

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