Crystal structure of Auer rods in acute myeloblastic leukaemia (AMyL).

Abstract

SUMMARY Ultrathin sections containing Auer rods from cases of acute myeloblastic leukaemia (AMyL) were tilted in the goniometer stage of the electron microscope and the resulting series of electronmicrographs analysed in an optical diffractometer illuminated by laser. The results showed that Auer rods of AMyL show a truly three dimensional crystal structure. Measurements from the optical diffraction patterns were consistent with a monoclinic unit cell, the unit cell edge lengths a, b, and c being 6-6 ((SD) 0 5) nm, 8-6 (0-2) nm, and 9-6 (1 0) nm, respectively; the angle between a and c being 120 (7)°. This structure was quite distinct from the "tubular" substructure reported by others in the Auer rods of acute promyelocytic leukaemia (APL), although it was consistent with periodicities measured by others in Auer rods of AMyL. A complete understanding of the three dimensional structures of Auer rods in the different types of acute myeloid leukaemia (AML) could well prove to be of considerable diagnostic importance.Auer rods, first observed at the beginning of the century by light microscopy,1 are cytoplasmic inclusions found only in the leucocytes of acute myeloid leukaemia (AML). It has been recognised for some time that at the ultrastructural level Auer rods often display internal periodicities2 4 and that their ultrastructure is different in acute promyelocytic leukaemia (APL) than in other subtypes of AML.56 It has never been formally shown, however, that Auer rods have true three dimensional crystal structures, and no attempt has been made to solve such structures. This paper presents the results of an initial study to investigate the three dimensional structure of Auer rods in acute myeloblastic leukaemia (AMyL), and a model for the structure is proposed. Studies of this type are important, not only to define accurately the ultrastructural differences that are already known to exist between the Auer rods of APL and the other subtypes of AML, but also to show any further ultrastructural differences, which may exist between Auer rods of the AML subtypes. Such differences would be of considerable diagnostic importance. Material and methodsClinical material used in this study was obtained from patients entered into the Medical Research Council 9th Acute Myeloid Leukaemia Trial. Aspirated bone Accepted for publication 8 January 1986 marrow from cases of AMyL was conventionally fixed and embedded in Spurr's resin.7 Briefly, leucocytes and marrow fragments were separated from erythrocytes by centrifugation after layering the aspirate on a solution of Ficoll-Hypaque as described by Swirsky et al.8 The leucocytes and marrow fragments remaining at the interface were washed twice in 0-1 M sodium cacodylate (pH 7.2) then fixed for one hour at room temperature in 1% glutaraldehyde, 0-1M sodium cacodylate (pH 7T2). The fixed cells were washed twice as above, post fixed in I % osmium tetroxide, 0-1M sodium cacodylate (pH 7-2) for 15 minutes at room temperature, and washed a further twice. Dehydration was through a grad...

Auer rod-like inclusions in multiple myeloma

“…At the ultrastructural level, Auer rods have been recognized as showing internal periodicities, which often correspond to the periodicities observed in primary neutrophil granules [7]. At the ultrastructural level, Auer rods have been recognized as showing internal periodicities, which often correspond to the periodicities observed in primary neutrophil granules [7].…”

Auer rods and faggot cells: A review of the history, significance and mimics of two morphological curiosities of enduring relevance

“…Auer rods in classical (hypergranular) APL are usually more prominent than in other types of AML. They also have a characteristic ultrastructural morphology, showing hexagonally arranged tubular structures with a specific 250 nm periodicity in contrast to Auer rods' 6–20 nm laminar periodicities in other AML subtypes 11,13 …”

“…They also have a characteristic ultrastructural morphology, showing hexagonally arranged tubular structures with a specific 250 nm periodicity in contrast to Auer rods' 6-20 nm laminar periodicities in other AML subtypes. 11,13 Rarely, MPO-negative APL occurs, either due to mutation in the gene encoding the enzyme or when the neoplasm develops in a person with congenital MPO-deficiency, a relatively mild immunodeficiency disorder. In such APL cases, the Auer rods are MPO-negative as well, and they are seen as thin, unstained areas (negatively-stained shadows).…”

Inzidenz und prognostische Bedeutung von Auerstäbchen bei Kindern mit akuter myeloischer Leukämie in den Studien AML-BFM-78 und -83*

“…Auerstäbchen sind nach deneitigen Kenntnissen als morphologischer Marker spezifisch für die AML und eng mit ihr verwandter Erkrankungen, wie das myelodysplastische Syndrom (3), das granulozytäre Sarkom (6) und die akute Basophilenleukämie (7). Wie histochemische und elektronenmikroskopische Untersuchungen gezeigt haben, entstehen Auerstäbchen aus den Iysosomalen Azurgranula der Granulozyten (1, 13), wobei licht-wie elektronenmikroskopisch die Bündel von Auerstäbchen bei der akuten Promyelozytenleukämie (19,26) von den Auerstäbchen in anderen AML-Subtypen (20,26) unterschieden werden können.…”