Search PubMed⌕ Search

Biomedical subjects

S Sacchi

Publications and source records attributed to S Sacchi.

95 records · Page 6Linked to original sources

Bcl-2 oncoprotein expression in acute myeloid leukemia.

BACKGROUND: In lymphoproliferative diseases the expression of Bcl-2, a mitochondrial oncoprotein capable of blocking apoptosis, is well-documented, while little research has been carried out on its distribution in myeloproliferative conditions. METHODS: Using immunocytochemical methods, 63 cases of acute myeloid leukemia (AML) at onset and 10 relapses were studied to investigate Bcl-2 expression and any possible correlations with subtypes of the FAB classification, sex, age or white cell peripheral blood count at onset. RESULTS: Bcl-2 is present in 87.3% of AML cases at onset and in 100% of relapses. In 68.3% of cases at onset and in 90% of relapses the protein is present in more than 20% of the blasts. Relapses always show higher percentages of positive expression than those seen at onset. Our results demonstrate no statistical correlations between the expression of the oncoprotein Bcl-2 and FAB subtypes, sex, age, or white cell peripheral blood count. CONCLUSIONS: The majority of blasts from AML patients express the oncoprotein Bcl-2, which is able to protect leukemic cells from apoptosis. Since numerous chemotherapies are cytotoxic in that they induce apoptosis, we feel that in vitro studies of cells from AML patients are necessary in order to broaden our knowledge about the effects of the most common therapeutic drugs and of those substances which, alone or in association, can modulate Bcl-2 expression.

Acute Disease↗

Myelodysplastic transformation in a case of essential thrombocythemia treated with pipobroman.

Essential thrombocythemia (ET) is a clonal disorder of the myeloid stem cell that causes pathologic expansion of the megakaryocytic elements in the bone marrow, with a persistent increase in the platelet count. In order to avoid the mutagenic effects of radioactive phosphorous and alkylating agents, various European clinicians use pipobroman rather than hydroxyurea as single chemotherapeutic treatment, since it is simple and well tolerated and does not lead to hematological complications or the risk of visceral cancer. Here we describe a 63-year-old ET patient who showed myelodysplastic transformation (RAEB-t) of the primary disease after about eight years of therapy with pipobroman at variable dosages.

Humans↗

All-trans retinoic acid in hematological malignancies, an update. GER (Gruppo Ematologico Retinoidi).

BACKGROUND AND OBJECTIVE: During the past ten years, the study of retinoids has undergone a total transformation. The Italian Society of Experimental Hematology decided to discuss these advances at a meeting in Florence on April 18, 1996. INFORMATION SOURCES: The material examined in the present review includes articles and abstracts published in journals covered by the Science Citation Index and Medline. In addition, all the authors of the present article have been actively working in the field of retinoids and have contributed several papers. Summaries of their oral presentations at the Florence meeting are reported in the Appendix to this review article. STATE OF ART AND PERSPECTIVES: One of the most important advances has been the elucidation of new molecular mechanisms of control of gene expression by retinoids. A number of new retinoids have been synthesized by chemists, some of which are being screened for potential clinical use, and a few have already had a tremendous impact on clinical practice. The most important achievements have been obtained in acute promyelocytic leukemia. In 1988 a Chinese group working in Shanghai showed that using all-trans retinoic acid (ATRA) alone 94% of acute promyelocytic leukemic patients obtained complete remission through differentiation of the leukemic clone. This result transformed a dream into reality and allowed researchers to move from laboratory experience to clinical applications of this differentiating therapy. Expanding the spectrum of hematological malignancies that may respond to ATRA remains a challenge; however, several results show some activity of retinoids alone or in combination with other drugs in juvenile chronic myeloid leukemia (CML), myelodysplastic syndrome, cutaneous T-cell lymphoma and CML. Particularly interesting are the studies that explored the potential clinical synergism of ATRA-based combination therapies with growth factors, other differentiating agents such as vitamin D3, immunomodulators like interferons, or chemotherapeutic agents, in particular Ara-C, all of which show promising in vitro effects when used in combination with retinoids.

Adult↗

Effects of interferon-alpha therapy on lymphocyte subpopulations in patients with chronic myeloid leukemia.

The mechanism of action of interferon-alpha (IFN-A) in chronic myelogenous leukemia (CML) is not known, but some evidence points at the immune modulation properties of IFN-A. We conducted a prospective analysis on 49 patients with CML in chronic phase treated with IFN-A in order to identify the effect of therapy on different lymphocyte subpopulations as determined by flow cytometric quantification and whether this effect is associated with the response to IFN-A. The absolute number of lymphocytes was similar in all patients regardless of response to IFN-A. In patients achieving a complete cytogenetic response (CCGR) there was a rebound of the absolute count of CD3+, CD4+, CD8+, and CD19+ lymphocytes after discontinuation of therapy with IFN-A. Patients with resistant disease, as well as patients with hematologic response but no cytogenetic response, showed a lower absolute number of CD19+ cells than patients with any cytogenetic response. Patients who achieved a CCGR had a higher absolute number of CD56+ cells than patients with lesser response or no response to IFN-A, and this persisted after discontinuation of therapy. We conclude that an increase in absolute number of CD19+ and CD56+ lymphocytes is observed in CML patients achieving a CCGR with IFN-A compared to patients with lesser responses. These changes could have functional consequences in the control of the disease.

Adult↗