Lymphocyte Production and Turnover

Perry, Seymour

doi:10.1001/archinte.1959.00270020052006

Cited by 17 publications

(7 citation statements)

References 23 publications

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“…In turn, the existence of a subset of MSC-mutated ISM patients showing only involvement of myeloid BM cells could be explained by preferential signaling of the mutated KIT in HPCs to the myeloid rather than the lymphoid lineages, the significantly different production and renewal rates of mature lymphocytes vs monocytes and neutrophils (longer vs shorter turnover times, respectively), or both. [55][56][57][58] In addition, occurrence of a sporadic KIT D816V mutation that constitutively activates the stem cell factor/KIT signaling pathway could lend those CD117…”

Section: Discussionmentioning

confidence: 99%

KIT D816V–mutated bone marrow mesenchymal stem cells in indolent systemic mastocytosis are associated with disease progression

Garcia-Montero¹,

Jara‐Acevedo

Álvarez‐Twose

et al. 2016

Blood

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Key Points• Acquisition of the KIT D816V mutation in an early pluripotent progenitor cell confers ISM cases a greater risk for disease progression.• Despite the early acquisition of the KIT mutation, onset of clinical symptoms of ISM is often delayed to middle adulthood.Multilineage involvement of bone marrow (BM) hematopoiesis by the somatic KIT D816V mutation is present in a subset of adult indolent systemic mastocytosis (ISM) patients in association with a poorer prognosis. Here, we investigated the potential involvement of BM mesenchymal stem cells (MSCs) from ISM patients by the KIT D816V mutation and its potential impact on disease progression and outcome. This mutation was investigated in highly purified BM MSCs and other BM cell populations from 83 ISM patients followed for a median of 116 months. KIT D816V-mutated MSCs were detected in 22 of 83 cases. All MSCmutated patients had multilineage KIT mutation (100% vs 30%, P 5 .0001) and they more frequently showed involvement of lymphoid plus myeloid BM cells (59% vs 22%; P 5 .03) and a polyclonal pattern of inactivation of the X-chromosome of KIT-mutated BM mast cells (64% vs 0%; P 5 .01) vs other multilineage ISM cases. Moreover, presence of KIT-mutated MSCs was associated with more advanced disease features, a greater rate of disease progression (50% vs 17%; P 5 .04), and a shorter progression-free survival (P £ .003). Overall, these results support the notion that ISM patients with mutated MSCs may have acquired the KIT mutation in a common pluripotent progenitor cell, prior to differentiation into MSCs and hematopoietic precursor cells, before the X-chromosome inactivation process occurs. From a clinical point of view, acquisition of the KIT mutation in an earlier BM precursor cell confers a significantly greater risk for disease progression and a poorer outcome. (Blood. 2016;127(6):761-768)

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Section: Discussionmentioning

confidence: 99%

KIT D816V–mutated bone marrow mesenchymal stem cells in indolent systemic mastocytosis are associated with disease progression

Garcia-Montero¹,

Jara‐Acevedo

Álvarez‐Twose

et al. 2016

Blood

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“…It is possible that these cells provide evidence of the seeding of lymphoid tissue from bone marrow or of seeding in the reverse direction. In dogs, Perry, Craddock, Paul and Lawrence (1959) were able to trace labelled thoracic duct cells to the bone marrow. Schooley and Berman (1960) described the transformation of labelled thoracic duct lymphocytes into monocytoid cells and plasma cells when cultured in vivo, either alone or with bone-marrow cells.…”

Section: Dna-synthesizing Cells In Venous Bloodmentioning

confidence: 99%

Quantitative Studies of Mitoses and DNA‐Synthesizing Cells in Bone Marrow and Blood of Guinea‐Pigs Recovering from Sublethal Whole‐Body Gamma Irradiation*

1963

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DIVISION by mitosis is confined to the more immature type of bone-marrow cell. However, the chances of observing mitoses in the least differentiated cells are considerably diminished by the low incidence of these cells in normal marrow.The study of the least differentiated cells may be fachtated by examining bone marrow in the early stages of regeneration after a temporary arrest of cell production. Provided that the arrest of haemopoiesis is of sufficient magnitude and duration, the more differentiated cells eventually mature and are discharged from the marrow. Then, until regeneration is relatively advanced, a period follows when immature cells predominate. Quantitative studies of bonemarrow in sublethally irradiated guinea-pigs (Harris, 1956(Harris, , 1960a have shown that immediately after an abortive recovery of granulopoiesis there is a short period between 12 and 14 days after irradiation, when immature cells are particularly evident and this precedes final erythropoietic and granulopoietic recovery. The proliferative activity of bone marrow at this early stage of regeneration has been studied before testing its ability to protect animals from the effects of a large dose of y-irradiation. Evidence that mitosis predominates in a particular cell group at this stage of regeneration would be of special interest.The purpose of this paper is to report quantitative studies of those cells in the bone marrow of young guinea-pigs which show evidence of proliferation at an early stage in the final recovery of haemopoiesis after sublethal whole-body irradiation. The identity of a cell may be more difficult to establish during mitosis but cells which are destined to divide can be easily recognized during the pre-mitotic stage of DNA-synthesis. Therefore, in each experiment, proliferation was studied by making concomitant observations of mitotic figures and DNA-synthesizing cells in smears prepared from the same sample of bone marrow. In addition, the size of each cell in mitosis or DNA-synthesis was recorded. Smears prepared from the buffy layer of centrifuged blood, obtained from the inferior vena cava, were examined for the presence of DNA-synthesizing cells.The discovery that bone-marrow cells from normal animals are able to colonize the haemopoietic tissues of lethally irradiated animals (Ford, Hamerton, Barnes and Loutit, 1956) emphasizes the need to identify the essential stem cells in bone marrow. The transplant may be of only short duration, being then replaced by the host's regenerating tissues, but the graft niay persist for a considerable time (Ford, 1961). The cells responsible for the persistence of a graft must be relatively immature and possess the ability to divide and to be a continuous source of progenitors. They could be blast cells which have already differentiated into early forms of granulocyte and red cell or, accepting the monophyletic theory of haemopoiesis, they might be cells of an even earlier order which still retain the ability to differentiate along various lines. The significance of the ...

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“…More recently it has been suggested that deoxyribonucleic acid (DNA) from phagocytosed lymphocytes can be used in the genesis of new lymphocytes (Hamilton, 1956;Trowell, 1957) and there is some evidence to suggest that DNA from lymphocytes may be used in the healing of skin wounds (Fichtelius and Diderholm, 1961). Some authors also visualize a trephocytic function for lymphocytes in relation to the growth of tumours and the proliferation of bone marrow and intestinal epithelium (Humble, Jayne, and Pulvertaft, 1956;Kelsau and Crabb, 1959;Perry, Craddock, Paul and Lawrence, 1959). This latter explanation was considered as an alternative to the 'lymphocyte-stem cell' hypothesis by Harris (1960b) when discussing haemopoietic recovery in the guinea-pig.…”

Section: Lymphocyte Morphology During Recoverymentioning

confidence: 99%

Lymphocytic Recovery after Irradiation and its Relation to Other Aspects of Haemopoiesise

Hulse

1963

Br J Haematol

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THE lymphocyte is a very radio-sensitive cell and tissues which contains lymphocytes, whether lymphopoietic or not, are markedly depleted of these cells, after exposure to even small doses of ionizing radiation. A quantitative study of the fall in the lymphocyte content of the bone marrow and blood of the irradiated rat has already been reported (Hulse, 1959a) and the present paper reports on their reappearance in these situations during recovery.One of the current theories of haemopoiesis suggests that the small lymphocyte is a multipotential stem cell (Yoffey, 1960a). The repopulation of bone marrow which has been depleted of cells by radiation is very suitable for testing such an hypothesis. The return of the lymphocytes to the depleted marrow has, therefore, been correlated with the recovery of erythropoiesis and myelopoiesis in the same animals. METHODA full description of the quantitative methods has been given in previous publications (Hulse, 1957(Hulse, , 1959a, the principle behind the marrow examination being the dispersion of a known quantity of femoral marrow in a suitable fluid. Blood examinations were performed on heart blood obtained at the time of killing the animals, immediately prior to extracting the marrow. Details regarding dosage of radiation and the type of rats used in the present investigation have already been given (Hulse, 1961). For each of the three doses used, 100,200 and 400 R., studies were made for 14,42 and 70 days respectively. In the figures (see below), the points relating to irradiated animals are means obtained from three (or in a few instances, four) rats. The data from unirradiated animals represent means from 41 rats, one animal from each litter being used as a control. RESULTSChanges in the blood and bone marrow during the first 48 hours after irradiation are reported first so that the present results may be compared later with those of the previous experiments (Hulse, 1959a). Initial DepletionMarrow lymphocytes. After each of three doses a minimum value was obtained at 2 days after irradiation, the reduction in cell numbers being least after IOO R. and greatest after 400 R. (Fig. I). At 48 hours after 400 R. the marrow lymphocytes were reduced to 13 per cent of normal but as early as 4 hours after irradiation they were reduced by as much as one-third. Thus the rate of depletion was greatest during the first few hours.Blood lymphocytes. These cells were reduced in number more than the marrow lymphocytes but minimum values were again obtained at 2 days ( Fig. I). Of these three doses 400 R. had the 3 76 * Postal address: M.R.C. Radiobiological Research Unit, Harwell, Didcor, Berks. Lymphocytes and Haernopoiesis ajier Irradiation3 77 greatest effect, the blood lymphocytes being reduced to 2.5 per cent or normal at 48 hours.As early as 4 hours after 400 R. they were reduced by two-thirds again indicating that the rate of depletion was greatest during the first few hours. RecoveryMarrow lymphocytes (Fig. I). Definite increases in numbers were seen at 3 days after roo and zoo...

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Lymphocyte Production and Turnover

Cited by 17 publications

References 23 publications

KIT D816V–mutated bone marrow mesenchymal stem cells in indolent systemic mastocytosis are associated with disease progression

KIT D816V–mutated bone marrow mesenchymal stem cells in indolent systemic mastocytosis are associated with disease progression

Quantitative Studies of Mitoses and DNA‐Synthesizing Cells in Bone Marrow and Blood of Guinea‐Pigs Recovering from Sublethal Whole‐Body Gamma Irradiation*

Lymphocytic Recovery after Irradiation and its Relation to Other Aspects of Haemopoiesise

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