Human megakaryoblastic proliferation and differentiation events observed by phase-contrast cinematography.

Microcinematographic documentation of mitoses, amitoses, endomitoses, or cytoplasmic fusion shortly after completion of mitoses was done in bone marrow specimens of patients with quantitative platelet disorders and controls. In patients with platelet disorders, most mitoses with cell duplication occurred in large promegakaryocytes after 4-fold nuclear and cytoplasmic enhancement. Normal specimens showed polyploidization happening in small megakaryoblasts, while mitoses with cell duplication were seen only after cultivation in freeze-thawed sera of patients with platelet disorders. Frequently, lymphocytes were observed to contact megakaryoblastic cells undergoing mitoses, amitoses and endomitoses and to enter the cytoplasm of megakaryocytes (emperipolesis), leaving it again after several hours.

Locomotion of human bone marrow and peripheral blood leukocytes is associated with maturational stage and altered in malignancy.

Using high-resolution phase contrast time-lapse microcinematography, slow movements (0.8-2.0 microns/minute) of human myeloblasts, monoblasts, and megakaryocytes can be recorded. Upon maturation to promyelocytes, motility is lost until cells have reached the stage of metamyelocytes (0.4 microns/minute). Motility increases sharply following maturation into segmented neutrophils (20.4 microns/minute). Monocytes and promonocytes display a mean track velocity of 7.1 microns/minute. The distribution of lymphocyte velocities is not bell-shaped but shows three maxima of 2.1 microns/minute, 7.8 microns/minute, and 18.4 microns/minute. Atypical lymphocytes from patients with infectious mononucleosis belong to the fast group, whereas lymphocytes activated in vitro by mitogens belong to the slow group. Red blood cell precursors from normal human bone marrow do not move actively. In contrast, erythroleukemic blasts show a motility comparable to normal myeloblasts. Similarly, acute promyelocytic leukemia cells move at 6.7 microns/minute, while their normal counterparts are sessile. Increased motility is also observed in blast cells from a variety of acute myelogenous and lymphoblastic leukemias.

Erythroblastopenia in two patients after splenectomy and polychemotherapy.

Acquired erythroblastopenia is a rare disorder of the hematopoietic system associated with viral infections, autoimmune diseases, and drugs. We report on two patients who became anemic due to maturation-arrest at the proerythroblast level, without alterations of white blood cell or platelet counts. Both patients had been splenectomized and had undergone chemotherapy for nephroblastoma or Hodgkin's disease, respectively, at the same pediatric oncology unit. Erythropoietin levels were elevated in both patients. Antibodies against specific viruses, particularly parvovirus B 19, could not be detected in patient sera. Both patients responded to infusions of 7 S immunoglobulin with a rapid increase of the reticulocyte counts. In both cases, complete clinical remission was observed after a duration of 5 months. Heat-inactivated serum obtained during the acute phase and after remission as well was found to be inhibitory for normal bone marrow granulocyte and erythrocyte progenitor growth in vitro. The simultaneous appearance of this rare disorder in two otherwise unrelated patients treated at the same unit prompts speculations about a viral etiology.

Syndrome of the posterior and anterior root in a late isolated CNS relapse of c-ALL. Case report.

A 15 year-old girl who had c-ALL diagnosed in 1982 was presented in our clinic suffering from an ascended flaccid paresis and dysaesthesia of both legs. These are typical symptoms of polyradiculitis of the nerve roots L2-S2. A lumbal puncture revealed a pleocytosis with lymphoblasts which were up to 40% CD10 (cluster of differentiation) up to 70% CD19 and TdT (terminal transferase) positive. The diagnosis of late isolated CNS relapse was made. It is assumed that local residual infiltrations of leukemic cells into the nerve roots L2-S2 got into cell cycle and caused these rare CNS leukemia symptoms. Therefore the value of a craniospinal irradiation to prevent a CNS and systemic relapse is discussed.

Calla-positive acute leukaemia with t(5q;14q) translocation and hypereosinophilia--a unique entity?

A patient with common acute lymphoblastic leukaemia (ALL), hypereosinophilic syndrome and t(5;14) (q31.1;q32.3) translocation is described. Even with intensive treatment only short periods of complete remission were achieved. Recurrence of the leukaemia was always accompanied by the appearance of eosinophilic granulocytes in the blood and in the bone marrow. Although there is no experimental proof we assume that the hypereosinophilic syndrome is causally related to the chromosome aberration. Translocation of the GM-CSF gene from chromosome No. 5 to chromosome No. 14, might have led to the deregulation of the gene by enhancer sequences of the immunoglobulin heavy-chain region on chromosome No. 14, with the consequence of an overproduction of neutrophilic and particularly eosinophilic granulocytes. Furthermore, stimulation of the leukaemic cell clone may have occurred by this translocation. The similarity of the clinical course with cases described in the literature suggests that this condition is a unique entity of ALL.

Measurements of nuclear sizes of committed hematopoietic progenitor cells compared to leukemic blasts from human bone marrow smears.

By measurements of the nuclear sizes of normal and of leukemic myeloblasts and monoblasts in colored smears, the differences estimated in surviving cells with phase contrast were confirmed. The median nuclear size of normal myeloblasts is the smallest one and differs significantly from that of the normal monoblasts and AML myeloblasts. The median nuclear size of normal monoblasts significantly exceeds values of normal myeloblasts and of AMoL monoblasts. Both leukemic blasts cover a wide range of nuclear diameters, but do not differ from one another, while normal myeloblasts have a smaller dispersion than normal monoblasts. The difference of leukemic blasts and normal progenitor cells is to be emphasized.

Lymphocytes as inducers of mitoses of human morphologically identifiable progenitor cells. Phase contrast observations.

Phase contrast time lapse observations of human bone marrow cells demonstrate the induction of progenitor cell mitoses or amitoses by the touch of locomotive lymphocytes on the cell surface. Interkinetic progenitor cells as well as precursor cells before mitosis were very rarely touched by lymphocytes. We suppose this cell-cell interaction is essential in the T-cell participation in hematopoietic stem cell proliferation.