Felice Gavosto

In-vitro effect of retinoic acid on normal and chronic myeloid leukemia granulopoiesis☆

The effect of increasing concentrations of retinoic acid (RA) on the in-vitro proliferation of normal and chronic myeloid leukemia (CML) granulo-monocyte precursors (CFU-GM) was studied. 10(-7)M RA added to semisolid cultures stimulated the growth of day 14 but not of day 7 normal CFU-GM, whereas in CML the growth of both populations was either unchanged or inhibited. Five-day and 10-day preincubation of normal bone marrow cells with RA augmented the number of day 14 CFU-GM (by up to 187% with 10(-6) M RA), whereas there was a marked decrease when CML cells were used. Total cellularity was not much affected, though a slight increase in liquid normal bone marrow cultures and a slight fall in CML cultures could be detected. These data point to a difference in the response to RA of normal and CML precursors. They may offer of preclinical basis for its employment to delay the blastic progression of CML.

In vitro incorporation of glycine-1-14C in reticulocytes

Abstract A β-ray track radioautographic study of the in vitro incorporation of glycine-1-14C in rabbit blood containing a high percentage of reticulocytes has been accomplished. Whereas the reticulocytes incorporate appreciable amounts of the amino acid, the mature erythrocytes have an activity not significantly above that of the background. If the reticulocytes are divided into the 4 Heilmeyer classes according to their degree of maturation, we have observed that the youngest have a much greater activity than the more mature ones.

MYELOFIBROSIS AND PROSTAGLANDINS: EFFECT OF PROSTAGLANDIN E1 ON COLONY‐FORMING CELLS (CFU‐GM)

Semisolid agar cultures of committed granulocyte monocyte precursors (CFU‐GM) make it possible to study the regulation of normal and abnormal stem cells. In vitro growth of CFU‐GM is dependent on the presence of specific stimulators, called CSA (colony stimulating activity) (Metcalf, 1977; Broxmeyer & Moore, 1978). The influence of CSA on CFU‐GM may be inhibited by prostaglandins of the E series (Broxmeyer & Moore, 1978; Kurland et al, 1978). Recently it has been demonstrated that chronic granulocytic leukaemia (CGL) CFU‐GM are insensitive to prostaglandin E1 (PGE1) over a wide range of concentrations that are inhibitory to normal CFU‐GM development (Aglietta et al, 1980; Pelus et al, 1980; Taetle & Koessler, 1980). We report the effect of PGE1 on CFU‐GM from patients with idiopathic myelofibrosis (MF).

Etude de l'action du shock sur la concentration en acides nucléiques des différentes fractions cytoplasmiques du foie

A traumatic shock decreases the ribonucleic acid content of the liver in the rat, as shown by both cytochemical and quantitative methods. In homogenates of the livers from the operated animals, the ribonucleic acid content increases in the supernatant after ultracentrifugation while it decreases in the mitochondrial fraction. The desoxyribonucleic acid is not affected by the traumatic shock.

Characteristics of cell proliferation in childhood lymphoblastic leukemias

The proliferative activity of the bone marrow and peripheral cells of acute infant lymphoblastic leukemia was evaluated by « in vitro » incorporation of thymidine-H3. The proliferative activity of leukemic lymphoblasts proved roughly similar to that already observed in hemocito-myeloblastic acute leukemias of adults. Within the lymphoblastic population, incorporation of tritiated thymidine was distributed very heterogeneously and there was no labelling of the smaller blasts. In the larger blasts, the labelling index increased progressively with the increase in cell diameter. The acute leukemia population can thus be divided into two classes: proliferating and non-proliferating. A study of the proliferative activity of lymphoblasts, contemporaneously in bone marrow and peripheral cells, suggested a division of cases into two groups. In one proliferative activity in the marrow was greater than in the peripheral blood; in the other it was equal to or less than in the peripheral blood. The second group was made up of cases whose clinical features presented a much more marked hepato-splenomegaly and high peripheral leucocytosis. A more detailed study of proliferative activity considering various classes of blasts within the same population showed that, in the first group of patients, the highest percentage of large blast cells is found at bone marrow level, while in the second the percentage of large blasts in the marrow is equal to or less than that observed in the peripheral blood. It was also shown that total proliferative activity is correlated to the percentage of large blasts. On the basis of these findings, one may admit that in first group forms the leukemia cells are generated prevalently in the bone marrow, while in second group forms most leukemic cells are formed elsewhere.

Induction of differentiation: a possible therapeutic approach to the treatment of hematologic malignancy

The most striking phenotypic abnormality in acute myeloid leukemia is the inability of the cells to differentiate into mature end cells. Because of an apparent uncoupling between proliferation and differentiation the cells remain in the proliferative pool and the neoplastic population greatly expands.

Different kinetic pattern of chronic myeloid leukemia: lymphoblastic and myeloblastic blastic crisis.

Cell kinetic studies were performed in 8 ease of lymphoid blastic crisis (BC) of chronic myeloid leukemia at the onset of BC and during subsequent relapses. The results were compared with those found in 7 myeloblastic BC. While in the myeloblastic transformation the labeling index (LI) was always higher in bone marrow than in peripheral blood blasts, suggesting a predominant bone marrow proliferation of the leukemic cells, in the lymphoid transformation a higher LI was often found in peripheral blasts. Moreover, the lymphoblastic transformations were frequently characterized by lymphadenopathy. These findings point to the similarities between lymphoid BC and acute lymphoblastic leukemia, suggesting the possibility that a blastic event may originate in an extramedullary site and that an extramedullary BC is more likely to be lymphoid in nature.

Changes in protein metabolism in proliferating and non-proliferating human acute leukaemia cells treated with actinomycin-D

Negli elementi blastici di leucemia acuta umana incubati in vitro viene osservato un dimezzamento delle sintesi proteiche fra la prima e la seconda ora di contatto actinomicinico. Uno stesso comportamento metabolico è stato rilevato negli elementi blastici proliferanti e non proliferanti.