Heterogeneity of Lymphocytes in Chronic Lymphocytic Leukæmia

Thomson, A. E. R.; Robinson, M M; Wetherley‐Mein, G.

doi:10.1016/s0140-6736(66)92480-9

Cited by 38 publications

(7 citation statements)

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“…The reduced lymphocyte transformation in CLL is the result of the presence in the circulation of an abnormal and slowly reacting population of leukaemic lymphocytes (Rubin et al, 1969) which dilutes the normal population of lymphocytes in tissue culture, rather than a reflection of the immunological status of the disease which depends upon the absolute numbers of immunologically competent cells available. A normal (PHAresponding) population of lymphocytes is present in CLL patients (Thomson et al, 1966), but is diluted by the large leukaemic cell population even though their absolute numbers seem to be preserved (Oppenheim et al, 1965;Hayhoe et al, 1967;Heine et al, 1969). This has also been demonstrated by the normalization of the lymphocyte transformation index after courses of splenic or total body irradiation, which selectively destroys the leukaemic (PHA non-responding) cells (Astaldi et al, 1966;Kagan and Johnson, 1967;Peckham and Parmentier, 1968).…”

Section: Discussionmentioning

confidence: 99%

“…THE in vitro lymphocyte response to specific or non-specific mitogens has been used as a measure of the ability of the lymphocyte to proliferate and as a reflection of its immunological function in vivo (Thomson, 1968;Ling, 1968;Roitt et al, 1969). Immunological abnormalities are among the main features of the immunoproliferative disorders, a heterogeneous group which includes the lymphoproliferative and plasma-cell disorders (Dameshek, 1970).…”

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confidence: 99%

“…An abnormal lymphocyte population, non-responsive or slowly responsive to mitogens, has been demonstrated in chronic lymphocytic leukaemia (CLL) (Quaglino and Cowling, 1964;Oppenheim et at., 1965;Thomson et al, 1966;Schrek, 1967;Lawler et al, 1968;Rubin et al, 1969). In CLL the percentage of blast transformation in response to phytohaemagglutinin (PHA) correlates inversely with the total lymphocyte count (Hayhoe et al, 1967) Leucocyte suspension cultures were set up in triplicate in bijoux bottles (Catovsky and Holt, 1970) (Naspitz and Richter, 1967;Catovsky and Holt, 1970).…”

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confidence: 99%

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Lymphocyte Transformation in Immunoproliferative Disorders

Catovsky¹,

Holt²,

Galton³

1972

Br J Cancer

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Summary.-Lymphocyte transformation with phytohaemagglutinin (PHA) was studied in 30 patients with immunoproliferative disorders (lymphoproliferative and plasma cell disorders).Lymphocyte transformation at 3 days was reduced in the lymphoproliferative disorders (chronic lymphocytic leukaemia (CLL), well-differentiated (lymphocytic) follicular lymphoma (FLL) and Waldenstrom's macroglobulinaemia (WM)), and normal in the plasma cell disorders (myelomatosis, primary systemic amyloidosis, a-chain disease and benign monoclonal gammopathy) and in idiopathic cold haemagglutinin disease. A case of plasma-cell leukaemia with increased numbers of abnormal cells in the circulation also showed reduced transformation. It is suggested that the presence in the circulation of abnormal lymphocytes (or plasma cells) accounts for the results in CLL and FLL, WM and plasma-cell leukaemia. In WM a correlation was found between the activity of the disease (expressed by the levels of IgM paraprotein) and the degree of blast transformation.The long-term (28 days) in vitro survival of lymphocytes using subconcentrations of PHA was also studied in 7 patients. The cell populations (PHA-non-responsive) of CLL and FLL, but not of WM, had a good in vitro survival, resembling in this respect the normal PHA-responsive population of lymphocytes, but they remained PHA-non-responsive after 4 weeks' culture. It is speculated that in CLL the long survival in vitro of the PHA-non-responsive (leukaemic) population corresponds to their long life-span in vivo.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Lymphocyte Transformation in Immunoproliferative Disorders

Catovsky¹,

Holt²,

Galton³

1972

Br J Cancer

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“…Lymphocyte separation was carried out by methods previously described (Thomson et al 1966a, Thomson & OConnor 1971 on freshly withdrawn blood following mechanical defibrination, except for one variation in the procedure as applied to leukaemic blood. Since some of the CLL-lymphocytes may be abnormally adhesive to polystyrene beads (Thomson et al 1966b) passage through a column of these was omitted and instead polymorphonuclear neutrophils (PMN) were removed magnetically. Carbonyl iron powder (type SF; Fine Dyestuffs & Chemicals Ltd., Manchester) was maintained in suspension in defibrinated blood (100 mg per 10-15 ml) for 30 min at 37" C (Kuper et al 1961) with a rotating mixer (Matburn Ltd., London).…”

Section: Methodsmentioning

confidence: 99%

Killing and Characterizing Action of Colchicine in vitro on Lymphocytes of Chronic Lymphocytic Leukaemia

Thomson

O'Connor

Wetherley‐Mein

1972

Scandinavian Journal of Haematology

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Circulating lymphocytes in chronic lymphocytic leukaemia (CLL) that die in vitro in 1 day of culture with 10‐7 M‐colchicine (0.04 μg per ml) have been classed as abnormal cells. Most of the increase in peripheral count in 30 patients so far tested (treated or untreated) is due to cells of this type. A colchicine concentration 100, 000 times greater (10‐2 M) kills peripheral populations from healthy individuals in one day. Use of nuclear pyknosis as the index of death has been validated by metabolic and ultrastructural examination of pyknotic lymphocytes. Kinetic studies suggest that initiation of pyknotic degeneration of an abnormal population is achieved at a colchicine concentration of 10‐7 M in ca. 10 hrs — or at higher concentrations in shorter times inversely related to concentration — after attainment of a seemingly critical level of colchicine binding by the population. From comparative cytocidal tests with several structural analogues, and with vinblastine, it is suggested that mode of cytocidal action of colchicine may have a biophysical basis like its antimitotic action involving binding in lymphocytes to micro‐tubular elements. One such analogue, trimethylcolchicinic acid methyl ether (NSC 36354) may be of therapeutic value in treatment of CLL.

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“…Die Bedeutung älterer biochemischer Studien mit ähnlichen Resultaten wird dadurch etwas eingeschränkt, dass sie nicht an rei nen Lymphozytenpräparationen vorgenommen wurden [1,3,14]. Die Aktivitätsminderung lysosomaler Hydrolasen lässt sich anderen Stoffwechseldefekten und funktionellen Störungen zuordnen, die bei CLL-Lymphozyten beschrieben wurden und diese Zellen als patho logischcharakterisieren [8,9,11,24,26,32,37,38,39,45,48,49,51].…”

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