A survey of 870 different adult blood samples (primarily from patients with non-haematological disorders) found that 269 (31%) had increased proportions (> 25%) and/or absolute numbers (> 1.0 x 10(9)/l) of morphologically-defined large granular lymphocytes (LGL), and/or phenotypically-defined NK-associated (NKa) cells. Of these, 112 were re-analysed at least 6 months after initial presentation and were classified as 'persistent' (92/112) or 'transient' (20/112) according to whether or not the original abnormality was still present. Lymphocyte counts in most patients with persistent abnormalities were within normal limits (18/92) or slightly increased (68/92), with only six having a lymphocytosis exceeding 10.0 x 10(9)/l. With the exception of five persistent LGL expansions in which the granular lymphocytes did not express NKa determinants (designated LGL+NKa-), the remaining 87 cases could be phenotypically grouped according to their primary abnormality as CD8+NKa+ (n = 33), CD4+ NKa+ (n = 14), CD8dim+NKa+ (n = 7) or CD8-NKa+ (n = 33). TCR genotypic studies in 58 patients showed that the 16 patients with rearranged TCR components were restricted to the CD8+NKa+ group and that, in most of these, the CD8+ fraction showed abnormal relative CD16/CD56 expression. Persistent neutropenia (n = 15) also appeared to be associated with primary abnormalities of CD8+NKa+ cells (12/15), with 10 of these additionally showing rearranged TCR genes. In contrast, persistently increased CD8dim+NKa+ and CD8-NKa+ components did not appear to phenotypically differ from their corresponding 'counterparts' in normal bloods or in patients with transient LGL/NKa+ abnormalities. This survey has therefore established that persistent LGL/NKa+ abnormalities are considerably more common than suggested in published work, that a high proportion of patients with expanded CD8+NKa+ components, with quite diverse clinical histories, show evidence of clonal lymphoid populations, and that the clonal nature of such disorders appears to be associated with abnormal NKa phenotypic patterns.
The myelodysplastic syndromes (MDS) are disorders in which the abnormalities are thought to be confined to cells of the myeloid series. However, examination of peripheral blood from 56 patients with MDS showed that the majority had low lymphocyte counts. In a detailed study of 2 5 patients, using OKT3, OKT4 and OKT8 monoclonal antisera together with SRBC rosettes, it was shown that there is a consistent and significant reduction in peripheral blood T lymphocytes. This decrease was primarily confined to the OKT4-defined helper subpopulation. There is a consequent relative increase in the OKT8-defined subset but in absolute numbers however, suppressor cells are reduced compared to normal particularly in those patients with lymphopenia. No correlations between T cell abnormalities and the different morphological groups of MDS were found. The possible implications of the reversed helper/suppressor ratio in the pathogenesis of MDS are discussed.
Acid alpha naphthyl acetate esterase (ANAE) and combined ANAE-chloroacetate esterase cytochemistry was performed on 121 bone marrow aspirates from primary myelodysplastic syndromes (MDS) and a secondary dysplasia-megaloblastic anaemia (MA). The investigation demonstrated the presence of abnormal ANAE positive granulocyte populations in a significant proportion of cases. These cells, in which the staining patterns were characterized by atypical granular ANAE positivity and double ANAE-chloroacetate reactions, were shown immunologically to lack the receptor and antigenic characteristics of monocytes and morphologically to be granulocytes. Isoelectric focusing, however, indicated that the atypical esterase cytochemistry of these granulocytes was due to the presence of markedly increased concentrations of ANAE isoenzymes usually found in monocytes. Atypical ANAE-staining granulocytes were particularly evident in MDS marrows showing sideroblastic erythroid changes, whilst in MA they were mainly seen in cases of intermediate severity. It is suggested that these cells are associated with dysmyelopoietic changes in both malignant and non-malignant conditions.
SUMMARY Membrane receptors for IgG and C3b were examined on blast cells from 57 cases of acute myeloid leukaemia. These acute leukaemias were classified as myeloblastic, myelomonocytic or monocytic following morphological, cytochemical, and immunological investigations. The membrane receptors of leukaemic blast cells appear to be directly related to the degree of monocytic differentiation with the lowest receptor activities found in acute myeloblastic leukaemia. A comparison was also made between receptor and cytoplasmic acid naphthyl acetate esterase (ANAE) activities in 29 morphologically and immunologically-defined myelomonocytic and monocytic leukaemias. This study revealed that the receptor-positive "monocytic component" in a significant proportion of cases showed unexpectedly weak or negative ANAE reactions suggesting a more cautious approach to the interpretation of ANAE cytochemistry in acute leukaemias. The normal development of cytoplasmic ANAE and membrane receptors is also discussed and compared with their abnormal patterns of expression associated with leukaemic transformation.The morphological classification of lymphoblastic leukaemias has been generally superseded by those based upon immunological characteristics.1-3 The lack of specific myeloid markers has, however, meant that the classification of acute non-lymphoid leukaemias has been largely dependent on morphological and cytochemical investigations.Previous
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