[Show abstract][Hide abstract] ABSTRACT: Systemic mast cell disease (SMCD) is a disorder characterized by a mast cell proliferation in various tissues. Mast cells express the c-kit proto-oncogene. A few cases of c-kit mutations have been described in SMCD. We report an aggressive SMCD in a patient who presented with a bone marrow infiltration by abnormal mast cells. Molecular studies of mast cell DNA and RNA revealed a new c-kit heterozygous mutation (Asp820Gly). This mutation leads to a drastic amino-acid change and is located close to the highly oncogenic Asp816Val. These findings suggest that the Asp820Gly has a potential role in c-kit activation.
British Journal of Haematology 03/1997; 96(2):374-6. · 4.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cytological analysis of peripheral blood and bone marrow films is a quick and simple method for diagnosis of acute leukemia. In association with cytochemistry techniques it allows the rapid identification and subsequent classification of most types of acute myeloid leukemias. Although morphological analysis can suggest the diagnosis of an acute lymphoblastic leukemia, it is necessary to have the corroborating evidence of immunological markers for confirmation. In addition, ultrastructural studies contribute to the identification of rare forms of acute myeloid leukemias (minimally differentiated, megakaryoblastic). Cytological studies have also proven useful for the follow-up activities of confirming complete remission and detecting relapses.
[Show abstract][Hide abstract] ABSTRACT: The diagnostic accuracy of a workstation for neoplastic bone marrow pathology was evaluated on 526 cases from two institutions. The workstation consists of knowledge-based systems for peripheral blood analysis, flow cytometry immunophenotyping, and bone marrow morphology, linked together by a relational database. The "gold standard" diagnosis was established by complete agreement among three hematopathologists after independent review of the data from each case. The workstation's diagnosis agreed with the "gold standard" in 515 cases (97.9%). In six of the 11 diagnostic errors, the bone marrow module could not reach a final diagnosis. The five misclassifications would not have resulted in a change of therapy for the patient. The institutional diagnosis of record agreed with the gold standard in 462 cases (87.8%). The results indicate that the workstation is capable of high-quality, reproducible, multiparameter interpretive reporting.
[Show abstract][Hide abstract] ABSTRACT: Flow cytometry (FCM) allows to measure the characteristics of individual cells. Cells in suspension are hydrodynamically focused in a laser beam. The emitted light signals give information on physical parameters and/or biological characteristics after the cells have been incubated with fluorescent reagents. FCM offers the possibility of a rapid, multiparametric analysis of a large number of cells. Hematology is one of the major fields of FCM applications.
FCM is the reference technique for total blood count. It is essential for immunophenotyping, measurement of DNA or RNA content and for analysis of cell functions. FCM and morphology are complementary for diagnosis and follow-up of hematologic disorders. FCM offers also cell sorting possibilities which are mainly used in basic research.
Revue Française des Laboratoires. 01/1995; 1995(275).
[Show abstract][Hide abstract] ABSTRACT: The development of high-grade non-Hodgkin's lymphomas in HIV-positive patients and patients with acquired immune deficiency syndrome (AIDS) is a well known phenomenon. The proper classification of these neoplasms often requires a multiparameter approach, including the interpretation of a large panel of immunologic markers analyzed by flow cytometry. The availability of individuals with the required expertise to properly interpret these marker studies is limited. For this reason, we have designed an expert system to automate the analysis of immunophenotyping panels in both HIV-related and non-HIV-related hematopoietic neoplasms. The expert system, which we call "Professor Fidelio", runs on IBM-compatible computers under Windows 3.0. The system is designed to accept any number of markers studied from a repertoire of 35 markers. Professor Fidelio functions on the basis of heuristic classification of defined diagnostic patterns. Nine specific patterns (Stem Cell, Myeloid and/or Monocytic, Erythroid, Megakaryocytic, Immature B-cell, Immature T-cell, Mature B-cell, Mature T-cell, and Plasma cell) and one "non-specific" pattern have been agreed upon. Fidelio's knowledge base contains the definitions of each of these patterns and the heuristics for excluding patterns when an incomplete panel of markers is performed. The inference engine interprets the findings (including the age of the patient) and reports the patterns which are matched, the differential diagnosis, the suggested diagnosis from the list of differentials if the marker studies are specific, and recommendations for additional tests which may be valuable in establishing the diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Journal of clinical computing 05/1994; 22(2-3):50-8.
[Show abstract][Hide abstract] ABSTRACT: We report the set-up of a denaturant gradient gel electrophoresis (DGGE) assay to screen for mutations in the whole coding sequence of the p53 gene. These DGGE experimental conditions were applied to the analysis of the p53 gene in acute leukemias. Forty adults with acute myelogenous leukemia (AML) and 21 with acute lymphoid leukemia (ALL) were investigated. Eleven of the AML patients were investigated at the time of the initial diagnosis and at relapse. In contrast with most reports based on amplified fragments analyzed by single-strand conformation electrophoresis and focusing on exons 5 to 8, we analyzed the whole coding sequence of the gene. Two of the 40 AML patients displayed a point mutation in exon 7; it was either an A to G substitution that converted Tyr-234 to Cys, or a G to A change that converted Arg-248 to Gln. The screening procedure led to the discovery of several intronic and exonic polymorphisms. These results confirm the low incidence of p53 mutations in acute leukemias and suggest a limited role of the p53 protein in leukemogenesis. The computerized modeling and electrophoresis parameters presented here provide a powerful tool for the exhaustive characterization of p53 mutants in all kinds of malignancies.
Human Mutation 02/1994; 3(2):126-32. · 5.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Twenty-six cases of adult T-cell leukemia/lymphoma (ATLL) were identified between 1983 and 1991 in Martinique (French West Indies). There were 14 men and 12 women, all of mixed racial descent and born in Martinique. Their ages ranged from 23 to 95 years. The main clinical and laboratory features at initial presentation were peripheral lymphadenopathy (22 cases), hepatomegaly (11 cases), splenomegaly (10 cases), cutaneous lesions (12 cases), hypercalcemia (16 cases), refractory infection by Strongyloides stercoralis (12 cases), and pre-existing autoimmune disorders (4 cases). All patients had absolute lymphocytosis with circulating pleomorphic abnormal lymphocytes. The prognosis was poor, with most patients (20 cases) surviving for less than 6 months. Although the overall clinicopathologic features of ATLL in this series are similar to those described in previous reports, we observed three additional points of interest: a high association with Strongyloides infection, an increased incidence of tropical spastic paresis/HTLV-1 associated myelopathy (TSP/HAM) among the relatives of the patients (5 cases), and the presence of prior collagen vascular diseases.
[Show abstract][Hide abstract] ABSTRACT: Acute myeloid leukemias (AML) and myelodysplastic syndromes (MDS) enter rarely in the differential diagnosis of myelofibrosis (MF). MF of marked intensity, resulting in either "dry taps" or non-representative smears, is encountered in approximately 10% of cases. MF may be observed in any type of AML, most frequently in acute megakaryoblastic leukemia (M7). Apart from some typical cases of MDS, MF is associated with cases of acute myelodysplasia with myelofibrosis (and a major megakaryocytic component). This syndrome has been described under various headings: acute or malignant myelosclerosis, and acute MF. It should be distinguished from M7 and from myeloproliferative syndromes.
Leukemia Research 02/1992; 16(1):51-4. · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Coulter VCS is a flow cytometer which performs, from a 100 microliter blood sample, a full five-part differential by assessing the volume (V), high frequency conductivity (C) and laser light scatter (S) on each white cell counted. The authors evaluated the Coulter VCS and compared its results with those of the Coulter STKR (three-part differential) and of the manual count. Reproducibility (ten replicate analyses on six different normal samples) was studied by the three methods and showed coefficients of variation closed to the manufacturer's specifications except for monocytes. The correlation coefficients obtained from 345 normal samples were the following: VCS/manual count: 0.97 for neutrophils, 0.70 for eosinophils, 0.97 for lymphocytes and 0.57 for monocytes; VCS/STKR: 0.99 for granulocytes, 0.99 for lymphocytes and 0.70 for monocytes. Comparisons of means displayed statistical differences for some cell categories but without clinical consequences. The flag analysis of 313 abnormal samples showed a false positive rate of 3.1 p. cent for the VCS and 1.8 p. cent for the STKR, the false negative rate was 2.1 p. cent for the VCS and 3.6 p. cent for the STKR. Starting from total blood count parameters, the authors propose guidelines for appropriate use of the different leucocyte differential methods.
Annales de biologie clinique 02/1990; 48(4):247-52. · 0.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: An expert system is described that includes interpretation of the results from a complete blood count as well as data from bone marrow aspiration. The system utilizes Bayes' rule. It has previously been tested on 180 cases of anemia including 20 benign and malignant hematologic disorders. On the data set, the system achieved 84% satisfactory diagnoses. In the present study, patients with myelodysplastic syndromes and with disorders of heme synthesis have been added to the test cases. For support, the expert system requires an IBM Personal Computer or equivalent. The program is available commercially (Coulter Electronics, Hialeah, FL).
[Show abstract][Hide abstract] ABSTRACT: We reviewed 213 consecutive adult pancytopenic patients to determine the frequency of underlying pathology, to analyze our diagnostic procedure, and to determine the value of peripheral blood data for diagnosis. Pancytopenia was defined as the association of hemoglobin level below 12 g/dl in males and 11.5 g/dl in females, leukopenia below 4 x 10(9)/L, and thrombocytopenia below 150 x 10(9)/L. The bone marrow aspirates were normo- or hypercellular in 140 cases (66%). Bone marrow biopsies, performed in 93 cases, documented the presence of myelofibrosis in 67 cases. Aplastic anemia was diagnosed in 10% of the cases. Malignant myeloid disorders (acute myeloid leukemias, myelodysplastic syndromes, acute myeloid disorders with myelofibrosis) represented 42% of the cases and various malignant lymphoid disorders 18%. Vitamin deficiencies accounted for 7.5% and nonhematological pathology 10% of the cases. The bone marrow aspirate was sufficient for the diagnosis in 55% of the cases, and the trephine biopsy was necessary in 30%. In the remaining cases, other complementary tests were necessary to achieve final diagnosis. A discriminant analysis, focused on the hemogram data, showed that parameters obtained by analysis of blood smears were helpful for the diagnosis, especially the presence or absence of blast cells and/or of abnormal lymphoid cells.
[Show abstract][Hide abstract] ABSTRACT: In this paper the characteristics and the effectiveness of a Baysian computer method applied to haematological diagnosis are analysed. The programme which is more effective than 2 clinicians recently trained in haematology can be used for teaching purposes.
Nouvelle revue française d'hématologie 02/1988; 30(1-2):51-3.
[Show abstract][Hide abstract] ABSTRACT: We have developed a new decision-making system which includes interpretation of complete blood count (CBC). The system works using Bayes' rule. We tested the CBC program for the diagnosis of 180 cases of anemia covering 20 benign and malignant hematological disorders. The data entered were obtained from a Coulter S + IV/HD and the interpretation of blood smears. Clinical information was not used. In 64.5% of cases, the correct diagnosis was displayed in first rank and in 20%, in second or third rank, giving a total of 84% of quite satisfactory responses. There were only 5% incorrect responses, but the proposed complementary tests rectified the error. Computer-aided diagnosis can help pathologists, clinicians, students, and technicians to make rapid correct diagnoses and choose the appropriate tests to perform. These programs run on IBM PC or similar microcomputers and are available from Coulter Electronics, Hialeah, FL.
[Show abstract][Hide abstract] ABSTRACT: A computer program to identify normal and pathological blood and marrow cells is presented. It requires an analysis of cellular morphology according to ten simple criteria. These criteria are treated by the Bayesian method; then the program offers, in decreasing order, the cells which are best classified. The responses are analyzed and discussed. This program seems to be well suitable to a computer-assisted teaching (CAT) of cytology. It supplements effectively the traditional methods.
Annales de biologie clinique 02/1987; 45(3):263-7. · 0.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The myelodysplastic syndromes (MDS) represent a group of syndromes having in common a defective production of one or more myeloid cell lines. They occur in patients which are more than 50 years old without any sex preponderance. The term MDS is replacing the obsolete and archaic term of 'preleukemia' and/or 'oligoblastic leukemia'. The more striking hematologic features are a discrepancy between a cellular bone marrow and a peripheral blood cytopenia. MDS may be idiopathic or secondary. Some of them precede or predispose to the subsequent development of an acute myeloid leukemia. A correct analysis of peripheral blood and bone marrow smears permits to classify MDS and to establish some prognostic features. Some syndromes are easily recognizable such as acquired idiopathic sideroblastic anemia, refractory anemia with excess of blasts, pure refractory cytopenia and acute myelodysplasia with myelofibrosis. Nevertheless this classification does not cover all these syndromes. Some of them with borderline features will be discussed separately. An analysis of a large series of MDS recently published in the literature will be presented as well as nosologic problems which arise. A conceptual effort should be made to recognize and evaluate the MDS.