TY - JOUR
T1 - Variations in ATM protein expression during normal lymphoid differentiation and among B-cell-derived neoplasias
AU - Starczynski, Jane
AU - Simmons, William
AU - Flavell, Joanne R.
AU - Byrd, Phillip J.
AU - Stewart, Grant S.
AU - Kullar, Harjit S.
AU - Groom, Alix
AU - Crocker, John
AU - Moss, Paul A.H.
AU - Reynolds, Gary M.
AU - Glavina-Durdov, Meri
AU - Taylor, A. Malcolm R.
AU - Fegan, Christopher
AU - Stankovic, Tatjana
AU - Murray, Paul G.
PY - 2003/8/1
Y1 - 2003/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0042346052&partnerID=8YFLogxK
U2 - 10.1016/S0002-9440(10)63672-3
DO - 10.1016/S0002-9440(10)63672-3
M3 - Article
C2 - 12875964
AN - SCOPUS:0042346052
SN - 0002-9440
VL - 163
SP - 423
EP - 432
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 2
ER -