Cell Proliferation in Leukemia during Relapse and Remission

Schmid, J.; Oechslin, R; Pg, Frick; Moeschlin, S

doi:10.1159/000209049

Cited by 14 publications

(2 citation statements)

References 9 publications

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“…In several studies evidence has been presented that the chance of re mission and survival time increases with a high labelling idex [10,22]. From these observations a good response to treatment would have been expected in the present case.…”

Section: Discussionsupporting

confidence: 63%

Cell Proliferation in the ‘Preleukaemic’ Phase of Acute Leukaemia

Queisser¹,

Olischläger²,

Queißer³

et al. 1972

Acta Haematol

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In a 13-year-old patient with acute leukaemia the leukaemic blast cells, the nucleated red cells and the megakaryocytes were studied by cytophotometrie determination of the DNA content and autoradiographic labelling with ³H-TdR invitro. In the preleukaemic phase a striking proliferation defect in the early polychromatic erythroblasts was observed, consisting of an accumulation of cells in G₁ and a decreased proportion of cells in S. In the megakaryocytes low DNA values from 2c-8c as compared to 4c-32c in normal megakaryocytopoiesis, and a decreased number of labelled cells between the ploidy stages was observed, indicating a severely restricted polyploidization capacity. These results suggest that in the preleukaemic stage a basic proliferation defect of acute leukaemic is becoming apparent in the so-called non-leukaemic cell systems, leading to peripheral mono- or pancytopenia.

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Section: Discussionsupporting

confidence: 63%

Cell Proliferation in the ‘Preleukaemic’ Phase of Acute Leukaemia

Queisser¹,

Olischläger²,

Queißer³

et al. 1972

Acta Haematol

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“…It has therefore become more and more desirable to find determinant initial factors related to possibly good or poor responses of the patients to cytostatic therapy. In the past, numerous investigators have stressed the therapeutic and prognostic significance of the pretreatment cytokinetics of malignant cells .19322, 24,27 Various study groups have postulated that high initial labeling and mitotic indices of leukemic blast cells correlated with successful treatment of adult acute myeloid leukemia (AML) 6,11,17,41,54 or acute lymphoblastic leukemia (ALL)15 while others have denied such a c~r r e l a t i o n .~~~~~~~~~~ This inconsistency in the medical literature concerns not only the predictive importance of cytokinetic factors, but also the prognostic implications of other initial parameters, e . g .…”

mentioning

confidence: 99%

Proliferation kinetics and cyclic amp as prognostic factors in adult acute leukemia

Paietta

Mittermayer

Schwarzmeier

1980

Cancer

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In 41 adult patients with acute leukemia (myeloblastic, lymphoblastic, and undifferentiated), proliferation kinetics (as determined by double-label autoradiography) and cyclic adenosine 3',5'-monophosphate (cAMP) concentration were studied for their significance in the prediction of responsiveness to cytostatic therapy. Patients with good clinical response had significantly shorter turnover times and higher labeling indices in the bone marrow than did those who failed to respond to treatment. Cases for which cell kinetics did not correlate with clinical response were explained by variance in the distribution of leukemic blasts between the proliferative cell cycle and the resting pool. Good clinical response was also found to be associated with low levels of cAMP in leukemic cells prior to therapy, whereas high cAMP contents predicted failure. Low cAMP concentrations, however, did not necessarily correlate with short turnover times and vice versa. This might be due to fluctuations of the cAMP concentrations during the cell cycle.

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Studies of cellular proliferation in human leukemia.III. Behavior of leukemic cells in three adults with acute leukemia given continuous infusions of3H-thymidine for 8 or 10 days

Clarkson¹,

Fried²,

Strife³

et al. 1970

Cancer

119

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Three adults with acute leukemia were given continuous infusions of 3H‐thymidine for 8 or 10 days. At the end of the infusions 88 to 93% of the leukemic cells were labeled. The leukemic cells varied in size and the flash 3H‐thymidine labeling indexes were generally progressively higher in direct relation to increasing nuclear size. Almost none of the smallest leukemic cells were labeled initially, but, at the end of the infusions, most were labeled regardless of size. The few remaining unlabeled were usually small, and it is concluded that these had remained dormant for die duration of the infusions. The mean generation time of the labeled fraction of leukemic cells in one patient was about 90 hours prior to treatment and about 200 hours during prednisone therapy. In the other 2 patients, antimetabolite therapy was started immediately after the infusions and the generation times were about 100 and 200 hours. There was considerable variability in generation time among the proliferating cells in each leukemic population. The minimum could not be determined because of continual interchange between cells of different sizes as a result of cell growth prior to division and halving of volume thereafter. The data is consistent with the hypothesis that the leukemic cells behave as a self‐maintaining population; we found no evidence for influx of leukemic “stem cells” from an unrecognized precursor compartment. In one patient, destruction of many of the leukemic cells by chemotherapy resulted in an increase in the 3H‐thymidine labeling index and the average size of the remaining cells. Similar findings have been described for several experimental tumors in vivo and for various cell types in vitro; i.e., their‐rate of proliferation varies according to their population density. Acute leukemic cells apparently grow less rapidly when their population density exceeds a critical level, but the finer alterations in kinetics which occur and the mechanism of growth inhibition are as yet unknown.

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Cell Proliferation in Leukemia during Relapse and Remission

Cited by 14 publications

References 9 publications

Cell Proliferation in the ‘Preleukaemic’ Phase of Acute Leukaemia

Cell Proliferation in the ‘Preleukaemic’ Phase of Acute Leukaemia

Proliferation kinetics and cyclic amp as prognostic factors in adult acute leukemia

Studies of cellular proliferation in human leukemia.III. Behavior of leukemic cells in three adults with acute leukemia given continuous infusions of3H-thymidine for 8 or 10 days

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