THE VALUE OF IMMUNOHISTOCHEMISTRY
IN THE ASSESSMENT OF BONE MARROW DISORDERS

Attilio Orazi, M.D., FRCPath. and Dennis P. O'Malley, M.D.

APOPTOSIS BY IN-SITU END LABELING The rate of cell death due to apoptosis can be evaluated by a nonisotopic in situ end-labeling (ISEL) technique applied to paraffin sections. Results from several groups including our suggest that an increased level of intramedullary apoptosis is apparent in both patients with MDS and those with AML; those with therapy-related disorders have the highest levels. In secondary AML and MDS cases, a correlation between high degree of apoptosis in myeloid cells and p53 overexpression was also demonstrated (Orazi et al, 1996). Controversial findings in lymphoid malignancy suggests that the apoptotic pathways may be different in this lineage. References Dar et al: Biological characteristics of myelodysplastic syndrome patients who demonstrated high versus no intramedullary apoptosis. Eur J Haematol. 1999;62:90-4. Greenberg P: Apoptosis and its role in myelodyslastic syndrome. Leuk Res. 1999 Sep;23(9):855. Irvine et al: Spontaneous intramedullary apoptosis is present in disorders other than myelodysplasia. Exp Hematol. 1998;26:435-9. Kurotaki et al:Apoptosis, bcl-2 expression and p53 accumulation in myelodysplastic syndrome, myelodysplastic-syndrome-derived acute myelogenous leukemia and de novo acute myelogenous leukemia. Acta Haematol. 2000;102:115-23. Orazi et al: p53 overexpression in myeloid leukemic disorders is associated with increased apoptosis of hematopoietic marrow cells and ineffective hematopoiesis. Mod Pathol. 1996 9:48-52. Novitzky et al: Increased apoptosis of bone marrow cells and preserved proliferative capacity of selected progenitors predict for clinical response to anti-inflammatory therapy in myelodysplastic syndromes. Exp Hematol. 2000;28:941-9. Parcharidou et al: Extensive apoptosis of bone marrow cells as evaluated by the in situ end-labelling (ISEL) technique may be the basis for ineffective haematopoiesis in patients with myelodysplastic syndromes. Eur J Haematol. 1999;62:19-26. Raza et al: Apoptosis in bone marrow biopsy samples involving stromal and hematopoietic cells in 50 patients with myelodysplastic syndromes. Blood. 1995, 86: 268-76. Raza et al: Excessive proliferation matched by excessive apoptosis in myelodysplastic syndromes: the cause-effect relationship. Leuk Lymphoma. 1997;27:111-8. Shetty et al: Intramedullary apoptosis of hematopoietic cells in myelodysplastic syndrome patients can be massive: apoptotic cells recovered from high-density fraction of bone marrow aspirates. Blood. 2000;96:1388-92. Shimazaki et al: Evaluation of apoptosis as a prognostic factor in myelodysplastic syndromes. Br J Haematol. 2000;110:584-90.