Bone marrow cell cycle markers in inherited bone marrow failure syndromes

Abstract

Patients with inherited bone marrow failure syndromes (IBMFS) are at increased risk of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), possibly related to cell cycle dysregulation. In a cross-sectional analysis of bone marrow from 77 IBMFS, 71 sporadic conditions (AML, MDS, acquired aplastic anemia) and 22 normal controls we found overexpression of p53 in IBMFS, AML, and MDS; of Ki-67 in IBMFS and AML; and of survivin in IBMFS compared with all other groups. The patterns of expression of cell cycle markers in IBMFS are thus distinct. Longitudinal studies will determine the diagnostic and prognostic significance of these findings.

Figure 1

Immunohistochemical stains in bone marrow biopsies. A. p53, 7% positive, from a patient with DC. B. Ki-67, 70% positive, from a patient with SDS. C. Survivin, 70% positive, from a patient with DBA. Original magnification X 500.

Figure 2

Expression of cell cycle markers. Each circle represents a patient; a filled circle represents a patient with IBMFS whose bone marrow also shows morphologic myelodysplasia. The dotted line corresponds to the highest expression of that marker in the normal group. Numbers below the X axis represent the rate of overexpression of each marker in each disorder. A. p53; B. Ki-67; C. Survivin. Abbreviations are defined in Table 1.

Figure 2

Expression of cell cycle markers. Each circle represents a patient; a filled circle represents a patient with IBMFS whose bone marrow also shows morphologic myelodysplasia. The dotted line corresponds to the highest expression of that marker in the normal group. Numbers below the X axis represent the rate of overexpression of each marker in each disorder. A. p53; B. Ki-67; C. Survivin. Abbreviations are defined in Table 1.

Figure 3

Combined expression of all three cell cycle markers. Left, controls: open circle, AML; red inverted triangle, MDS-hi; green square MDS-lo; yellow diamond, AA; and black triangle, normal. Right, IBMFS: white circle, FA; red circle, DBA; green circle, SDS; yellow circle, DC. Loops indicate those with low (blue), intermediate (black), and high (red) expression of survivin.