A diploid epithelial cell line from normal adult rat liver with phenotypic properties of ‘oval’ cells

Retrospective analysis of patients with acute myelomonoblastic (or non-lymphocytic) leukemia has helped to clarify the early stages of the evolution of this disease, and a clinical picture has emerged that is sufficiently discriminating to permit prospective observations. The clinical and laboratory features of the hematologic disorder preceding overt, blast-cell leukemia (i.e., the “preleukemic syndrome” or “hemopoietic dysplasia”) are described, and diagnostic criteria and approaches to management are considered. This hematologic syndrome appears to be a stage in a multiphasic panmyelopathy that involves all products of the marrow stem cell. Available data indicate that most of these patients develop acute leukemia within 24 months of the onset of the hematologic abnormalities, but longer courses are not uncommon. Prospective documentation in a large group of patients is needed before the natural course can be accurately defined; such studies are now being planned.

The preleukemic syndrome (hemopoietic dysplasia).

Pyruvate kinase (ATP: pyruvate phosphotransferase, EC 2.7.1.40, PK) deficiency associated with hereditary nonspherocytic haemolytic anaemia was first reported in 1961 (Valentine et al, 1961). I t has become increasingly apparent that most, if not all, cases of PK deficiency are caused by the production of mutant enzymes with abnormal characteristics. A variety of techniques and methods have thus far been used in different laboratories for characterizing PK variants. The use of standard methods for the analysis of PK variants would make it possible to compare results obtained in different laboratories, and to identify variants on the basis of biochemical parameters as well as clinical manifestations. Such methods have been developed through a collaborative effort among members of a working group of the ICSH Expert Panel on Red Cell Enzymes, and comprise the major part of this report. As far as possible, a common buffer system, substrate and co-factor solution are proposed in order to simplify the methodology as well as the interpretation of data. The number of essential parameters for abnormal PK are minimized because of the limitation of both time required for the studies and volume of blood obtainable from a patient. This does not imply that other procedures such as urea stability (Koster et a l , 1971; Miwa et al , 1975), alanine inhibition (Staal et al, 1976), immunological methods (Lincoln et al , 1975; Miwa et al , 1975; Kahn et a l , 1976), isoelectric focusing (lbsen & Trippet, 1971; Kahn et al , 1976; Oda et a l , 1976), etc., are unimportant. Rather, it is suggested that these other studies be done optionally for further understanding of the abnormal characteristics of the variant enzymes.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2141.1979.tb03751.x

Recommended Methods for the Characterization of Red Cell Pyruvate Kinase Variants

Publisher Summary This chapter describes enzyme alterations in some selected systems. The isocitrate lyase from old Turbatrix aceti ( T. aceti ) consists of a mixture of active and inactive molecules. The nematode T. aceti , the eye lens, and red blood cells are the systems that allow recognition of the most frequent and unequivocal postsynthetic changes in enzymes. G6PD shows two types of modifications: (1) a nonproteolytic lowering of the isoelectric pH and (2) a limited proteolysis of the COOH-terminal end, which takes place in the red blood cells. Aldolase undergoes a specific deamidation. Changes in enzyme level and properties can be because of changes in rates of proteolysis. Salivary amylase in humans is present as multiple isozymes, which is derived from a single gene product through posttranscriptional modifications. The lens of the eye is a very peculiar organ in many respects. It is a nonvascularized tissue, receiving nutrients from aqueous and vitreous humors. It is an organ of choice in the study of some aspects of postsynthetic changes in proteins.

Posttranslational modifications of enzymes.

The genetic system of the L-type pyruvate kinase forms in man. Subunit structure, interrelation and kinetic characteristics of the pyruvate kinase enzymes from erythrocytes and liver.

Summary. 

Enzyme abnormalities are frequently found in the red cells of patients with various acquired blood disorders. In leukaemias, preleukaemic states and bone marrow insufficiencies with or without sideroblastosis, changes in enzyme activity are usually characterized by the coexistence of deficiency of some enzymes and an increased activity of others.



The most frequently decreased activities are those of pyruvate kinase, phosphofructokinase,2,3-diphosphoglycerate mutase and adenylate kinase; the most frequently increased activities are those of hexokinase, aldolase, enolase, 6-phosphogluconate dehydrogenase and glucose-6-phosphate dehydrogenase.



In primary myelofibrosis and in polycythaemia rubra vera, enzyme deficiencies are infrequent and differ from those observed in leukaemias and related disorders. Phosphohexose isomerase and phosphoglucomutase deficiencies seem relatively specific for polycythaemia rubra vera.



Explanations for the acquired enzymopathies are still at the stage of hypothesis. The theory of multiple genetic damage may explain some findings but has not yet been proved right. The possibility of post-translational molecular modification is suggested as a working hypothesis.

Acquired erythroenzymopathies in blood disorders: study of 200 cases.

Erythrocyte pyruvate kinase (PK) from 5 patients with congenital non-spherocytic hemolytic anemia and erythrocyte PK deficiency have been studied by immunological methods and electrofocusing.

Colette Galand

Papers

Acquired erythroenzymopathies in blood disorders: study of 200 cases.

Molecular mechanism of erythrocyte pyruvate kinase deficiency

Human erythrocyte phosphoglycerate kinase deficiency: presence in a deficient patient of a stable variant with lowered catalytic activity.

Isoelectric focusing of spectrin components in hereditary spherocytosis.