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2  /  Chapter 1  Haemopoiesis



                       Th is first chapter is concerned with the general   marrow consists of fat (Fig.  1.1 ). Th e  remaining
                    aspects of blood cell formation (haemopoiesis). Th e   fatty marrow is capable of reversion to haemopoiesis
                    processes that regulate haemopoiesis and the early   and in many diseases there is also expansion of
                    stages of formation of red cells (erythropoiesis),   haemopoiesis down the long bones. Moreover, the
                    granulocytes and monocytes (myelopoiesis) and   liver and spleen can resume their fetal haemopoietic
                    platelets (thrombopoiesis) are also discussed.          role ( ‘ extramedullary haemopoiesis ’ ).

                        Site of  h aemopoiesis                    Haemopoietic  s tem and
                                                                p rogenitor  c ells
                      In the first few weeks of gestation the yolk sac is the

                    main site of haemopoiesis. However, defi nitive hae-    Haemopoiesis starts with a pluripotential stem cell
                    mopoiesis derives from a population of stem cells   that can self - renew but also give rise to the separate

                    first observed on the dorsal aorta termed the AGM   cell lineages. These cells are able to repopulate a

                    (aorta - gonads - mesonephros) region. Th ese common   bone marrow from which all stem cells have been
                    precursors of endothelial and haemopoietic cells   eliminated by lethal irradiation or chemotherapy.
                    (haemangioblasts) are believed to seed the liver,   Th is  haemopoietic stem cell  is rare, perhaps 1 in
                    spleen and bone marrow and from 6 weeks until   every 20 million nucleated cells in bone marrow.
                    6 – 7 months of fetal life the liver and spleen are the   Although its exact phenotype is unknown, on
                    major haemopoietic organs and continue to produce   immunological testing it is CD34    CD38    and
                                                                                            +
                                                                                                   −
                    blood cells until about 2 weeks after birth (Table   negative for lineage markers (Lin  ) and has the
                                                                                           −
                     1.1 ; see Fig.  7.1 b  ). The bone marrow is the most   appearance of a small or medium - sized lymphocyte

                    important site from 6 to 7 months of fetal life.   (see Fig.  23.3   ). The cells reside in specialized   niches ’ .
                                                                                               ‘

                    During normal childhood and adult life the marrow   Cell differentiation occurs from the stem cell via

                    is the only source of new blood cells. Th e develop-  committed  haemopoietic progenitors  which are
                    ing cells are situated outside the bone marrow   restricted in their developmental potential (Fig.
                    sinuses; mature cells are released into the sinus    1.2 ). The existence of the separate progenitor cells

                    spaces, the marrow microcirculation and so into the   can be demonstrated by  in vitro  culture techniques.
                    general circulation.                      Very early progenitors are assayed by culture on
                        In infancy all the bone marrow is haemopoietic   bone marrow stroma as long - term culture initiating
                    but during childhood there is progressive fatty   cells whereas late progenitors are generally assayed
                    replacement of marrow throughout the long bones
                    so that in adult life haemopoietic marrow is con-

                    fined to the central skeleton and proximal ends of
                    the femurs and humeri (Table  1.1 ). Even in these
                    haemopoietic areas, approximately 50% of the





                         Table 1.1   Sites of haemopoiesis.
                         Fetus     0 – 2 months (yolk sac)
                                 2 – 7 months (liver, spleen)
                                 5 – 9 months (bone marrow)
                         Infants     Bone marrow (practically all bones)


                                                                        Figure 1.1   A normal bone marrow trephine biopsy
                         Adults     Vertebrae, ribs, sternum, skull,
                                                              (posterior iliac crest). Haematoxylin and eosin stain;
                               sacrum and pelvis, proximal ends
                                                              approximately 50% of the intertrabecular tissue is
                               of femur
                                                              haemopoietic tissue and 50% is fat.
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