Fetal bone marrow: the size, number and spatial distribution of CD34+ cells

It is thought that almost all childhood leukaemia is initiated in the fetus. The target cells for the induction of leukaemia are found predominantly in the bone marrow. We are investigating the part played by natural background alpha-radiation in utero in the onset of childhood leukaemia. One application we are following is to estimate the risk of leukaemia from natural alpha-radiation and for this we need to know about the size and location of the target cells within normal fetal bone marrow.

In contrast to adult bone marrow, fetal bone marrow does not contain fat cells. It has been shown that 210Pb is taken up into fetal bone as it follows the uptake of calcium during calcification of the skeleton. In addition, the marrow spaces in fetal trabecular bone are much smaller than those in the adult. 210Po concentration has been measured in autopsy bone samples and comes mainly from the decay of 210Pb at bone surfaces. The small sizes of the trabecular spaces, together with the relatively higher activity concentration levels for 210Po in bone samples compared to soft tissues indicates that the alpha-emitting 210Pb-supported 210Po at bone surfaces may be the most important natural radionuclide for irradiation of fetal bone marrow.

CD34+ cells (brown ringed) in fetal bone marrow

CD34+ cells in fetal bone marrow

The cells at risk of leukaemogenesis are the haemopoietic stem cells and from about 14 weeks gestation, they are present in the bone marrow. Several studies have inferred that childhood leukaemia (ALL) is initiated in utero. The COMARE Fourth Report has estimated that about 14% of childhood leukaemia is linked to natural high-LET (alpha-) radiation. Further, an estimated 9% of ALL is thought to be due to the radioactive decay of 210Po which is supported by 210Pb deposited in bone.

CD34+ cell near bone surface

CD34+ cell near a bone surface

The alpha-radiation dose received by fetal bone marrow and the haemopoietic stem cells from natural alpha-emitters was, until recently, unknown. In order to estimate the alpha-radiation dose to these cells, thin sections of normal fetal bone marrow were stained with monoclonal antibody CD34. The (i) size, (ii) number and (iii) spatial distribution of the CD34+ cells was determined. The information was used in Monte Carlo simulations of alpha-particle tracks to determine the Linear Energy Transfer (LET) at which the alpha-radiation doses are delivered to the marrow and to the haemopoietic stem cells.

Reference

An in situ study of CD34+ cells in human fetal bone marrow
Janet E Allen and Denis L Henshaw, 2001British Journal of Haematology 114, 201-210

Natural alpha-emitters in fetal dosimetry
Purnell SJ, Allen JE, Oyedepo AC and Henshaw DL, 1999 Radiation Research 152, S133-S136