Recurrent mutations in the iron regulatory element of L-ferritin in hereditary hyperferritinemia-cataract syndrome.

Background And Objective: Hereditary hyperferritinemia-cataract syndrome (HHCS) is an autosomal dominant disorder characterized by bilateral cataracts and increased serum and tissue L-ferritin, in the absence of iron overload. The deregulation of ferritin production is caused by heterogeneous mutations in the iron regulatory element (IRE) of L-ferritin that interfere with the binding of iron regulatory proteins.

Design And Methods: We have identified several patients from three unrelated Italian families with HHCS.

Effect of interferon-gamma on HLA class II antigen expression and sensitivity to prostaglandin E1 by normal and leukemic myeloid progenitors.

Chronic myelogenous leukemia (CML) granulo-monocyte committed progenitors (CFU-GM) are markedly less sensitive than normal progenitors to the inhibitory action of prostaglandin E (PGE). This phenomenon has been ascribed to their abnormal expression of HLA class II (mainly DR) determinants. Since interferon gamma (IFN-gamma) is a potent inducer of the expression of HLA class II (DR and to a lesser extent DQ) antigens, we have sought to determine the extent to which this agent can modulate both the antigenic pattern of normal and leukemic progenitors and their sensitivity to PGE 1.

Expression of HLA class II determinants by normal and chronic myeloid leukemia progenitors.

It has been suggested that the expression of some HLA class II antigens, derived from three loci (DR, DP, DQ) is important in the regulation of both the immune response and the response of haemopoietic progenitors to regulation factors, such as acidic isoferritins (AIF), as well as in the interaction between T lymphocytes and erythroid progenitors (BFU-E). Changes in the expression of class II antigens have been reported on the surface of granulo-monocyte progenitors in chronic myeloid leukemia (CML) and correlated to the abnormal proliferation of such cells. In this study, monoclonal antibodies against DR and DQ monomorphic determinants were used to investigate the expression of these antigens on the surface of normal and CML bone marrow and peripheral blood BFU-E by means of complement mediated cytotoxicity.

A short-term chemosensitivity test with different labeled precursors of DNA or protein synthesis: correlation with clinical response.

Blood or bone marrow samples from 15 patients with newly diagnosed acute myeloblastic leukemia undergoing remission induction treatment with daunorubicin, cytosine-arabinoside and 6-thioguanine were tested in vitro. Leukemic cells were incubated for 24 h at 37 degrees C with or without the drugs alone or in combination. A 3-h pulse with labelled precursors of DNA synthesis (3H-thymidine) or protein synthesis (3H-leucine) was then given separately.

Peripheral erythroid precursor and prognosis in chronic granulocytic leukemia.

Seventy-four consecutive patients with nonblastic chronic granulocytic leukemia (CGL) were observed from diagnosis and retrospectively studied. The patients were segregated into three risk groups according to the staging system proposed by Sokal et al. A significant difference in survival was observed only between Stage I and III (P = 0.

Expression of HLA class II (DR, DQ) determinants by normal and chronic myeloid leukemia granulocyte/monocyte progenitors.

It has been suggested that the expression of certain HLA class II antigens stemming from three distinct loci (DR, DP, and DQ) is important not only in the regulation of the immune response but also on the response of hemopoietic precursors to factors inhibiting myelopoiesis. Changes in the expression of DR antigens may be involved in the pathogenesis of altered cell proliferation in chronic myeloid leukemia, since they result in decreased sensitivity of the colony forming units, granulocyte-macrophage to prostaglandin E and acidic isoferritins. In studies using monoclonal antibodies against monomorphic DR or DQ determinants, in a complement-dependent cytotoxic assay, it was found that nearly all normal and chronic myeloid leukemia bone marrow colony forming units, granulocyte-macrophage express DR antigens.

Adenosplenomegaly and prognosis in uncomplicated and complicated chronic lymphocytic leukemia. A study of 362 cases.

Presence and size of lymph nodes and spleen, graded from 0 to , in 362 patients with CLL observed from diagnosis were evaluated. Statistical analysis showed a relationship with age, sex, anemia and thrombopenia, leukocytosis, and outlined two different groups: the one without organomegalies , with higher mean age (67 years), female prevalence, and better prognosis; the other with adenosplenomegaly graded ++/ , with lower mean age (57 years), clear male prevalence, and worse prognosis. Survival results were statistically different only between groups 0/+ versus group ++/ .

Immune-complexes (IC) in idiopathic neutropenia.

The presence of immune-complexes (IC) and antipolymorphonuclear neutrophil (PMN) autoantibodies was investigated in 28 patients with chronic idiopathic neutropenia and normal or hypercellular bone marrow, 19 with a metamyelocyte arrest and 9 with more dysplastic features. The in vivo interaction between IC and PMN membrane receptors was evaluated by means of the PMN immunohistological technique. Circulating IC was evaluated with the C1q and rheumatoid factor agglutination inhibition techniques.

[Adenopathies in chronic myeloid leukemia (CML). Study of 161 cases].

161 cases of CML have been studied. Clinically significant adenopathies were present in 3,2% of the patients at the moment of diagnosis, and in the subsequent course they appeared in 7% of them. The behaviour of adenopathies showed to be unrelated to: --splenomegaly; --blastic metamorphosis in the peripheral blood or in the marrow (which they often preceded from 3 to 26 months); --hematological sensibility to cytostatic therapy; and furthermore they often acted as the most important clinical and therapeutic problem.

Chronic lymphoid leukemia. Clinical observations about its natural progression.

223 cases with chronic lymphoid leukemia (CLL) were subjected to a prospective study on the presence of adeno- and splenomegaly at diagnosis and their subsequent variation. Subjects with no initial organ involvement were usually female (76%) and of old age (mean 69.2 years).

[Association of leukemias and tumors. Studies of 502 cases of leukemia].

Nineteen association of leukaemia and tumour were noted in a series of 502 cases of leukaemia: 12/180 (6.6%, compared with 4.7% of 5136 cases in the liteature) for Chr.

[Acute leukemia. Case material and therapeutic results].

In the five years period 1969-1973, 22 cases of acute lymphoblastic (ALL) and 75 of acute myeloid leukaemia (AML) were observed in adults. In ALL, complete remission was obtained in 61% of cases. The median duration of remission worked out to be 3 months in the group of patients who died and more than 6 months in the patients still alive.

Treatment of acute myeloid leukaemia according to the Hammersmith protocol: preliminary report.

A preliminary report is given of a trial of the T.R.A.