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Biomedical subjects

M T Daniel

Publications and source records attributed to M T Daniel.

At least 109 records · Page 6Linked to original sources

Cytogenetic studies on acute myelomonocytic leukaemia (M4) with eosinophilia.

Cytological and cytogenetic studies on 17 acute myelomonocytic leukemia with bone marrow eosinophilia (M4EO) are reported. Cytological criteria include an unusual high proportion of eosinophilic cells containing abnormal granules. Abnormal karyotypes have been found in 12 patients but chromosome 16 abnormalities were present in only 9. In two of them only one such mitosis was detected whereas in 7 others inv(16)(p13q22) and/or del (16)(q22) clones were present. However in 16 cases normal karyotypes were also present. Other abnormal clones coexisted in three patients, suggesting that chromosome 16 abnormalities are not linked to a primary leukemogenic event. M4EO was found to be associated with a favourable prognosis.

Adolescent↗

Criteria for the diagnosis of acute leukemia of megakaryocyte lineage (M7). A report of the French-American-British Cooperative Group.

For the diagnosis of M7, the bone marrow aspirate shows a leukemic cell infiltrate that comprises 30% or more of all cells. These cells are identified as being of megakaryocyte lineage by the platelet peroxidase reaction on electron microscopy or by tests with monoclonal or polyclonal platelet-specific antibodies. Myelofibrosis or increased bone marrow reticulin are a prominent aspect in most patients with M7. In patients with increased reticulin, the bone marrow sample may be difficult to obtain and the counts done on the marrow films may be misleading. In these patients, the diagnosis of M7 should be based on excellent bone marrow biopsy sections that show an excess of blasts and, at times, increased numbers of maturing megakaryocytes; and on the presence of unequivocal megakaryoblasts in the peripheral blood or bone marrow (or both) as shown by immunologic techniques.

Acute Disease↗

[Acute myeloblastic leukemia with involvement of the basophilic cell line and anomalies of the short arm of chromosome 12 (12p)].

Among 16 leukemia patients with abnormalities of the short arm of chromosome 12 (12p) were found 5 patients with an increased number of marrow basophils and a special M2 cytological feature. This new correlation between 12p abnormalities and M2-baso phenotype is presented. The localisation of c-k ras 2 genes at the same 12p site suggests a possible mutation of this c-oncogene.

Basophils↗

Promyelocytic blast crisis of chronic myelocytic leukemia with both t(9;22) and t(15;17) in M3 cells.

A blast crisis with the features of promyelocytic leukemia (M3) occurred during the evolution of chronic myelocytic leukemia (CML) with the t(9;22) translocation. This rare form of transformation was confirmed by means of cytologic and electron microscopic examination. Cytogenetic studies showed two simultaneous translocations t(15;17) and t(9;22) in the promyelocytes. After intensive chemotherapy, a complete remission was obtained and only karyotypes with t(9;22) translocation were present. These data confirm the specificity of the t(15;17) translocation in malignant promyelocytic proliferation and provide evidence for a second genetic event in the genesis of blast crisis occurring in a committed cell belonging to the abnormal population defined by the Ph1 chromosome.

Bone Marrow↗

Malignant lymphomas with band 8q24 chromosome abnormality: a morphologic continuum extending from Burkitt's to immunoblastic lymphoma.

Chromosome abnormality involving band 8q24 is present in the malignant cells in virtually all 'Burkitt's' type malignancies. t(8;14)(q24;q32) translocations have nevertheless been found in certain cases of malignant lymphomas (ML) described as 'small non-cleaved non-Burkitt', 'immunoblastic' or 'histiocytic'. With a view to comparing objectively the histological picture of such lymphomas, we undertook morphometric analysis of seven cases of diffuse ML classed as 'Burkitt's' (three cases), 'immunoblastic' (two cases), 'small non-cleaved non-Burkitt' (one case) and 'large-cell lymphoma' (one case), all exhibiting band 8q24 rearrangement arising from various translocations. Our study substantiates the view that the histologic picture of MLs with 8q24 anomaly fits into a morphological continuum containing 'Burkitt's', 'small non-cleaved non-Burkitt' and 'immunoblastic' lymphomas.

Adult↗

Acute monoblastic leukaemia. Clinical, biological data and survival in 45 cases.

Between 1978 and 1980, 45 cases of acute monoblastic leukaemia have been diagnosed, treated and followed in our institute. Morphological diagnosis was performed according to the French-American-British classification. Tumoral syndrome (particularly extra-medullary) and hyperleucocytosis were the most striking findings at the time of diagnosis. Cytogenetic analysis performed in 31 cases before treatment has showed that abnormality of the long arm of chromosome 11 seemed to be more frequently associated with the poorly differentiated cytological subtype M5 (a). Intensive chemotherapy with zorubicin and cytosine arabinoside led to complete remission in 75% of the cases. Central nervous system prophylaxis appeared definitively useful in preventing meningeal relapse. Despite a prolongation of the median duration of complete remission which now reaches 12 months, the prognostic is still poor.

Adolescent↗

Cytological types of mitoses and chromosome abnormalities in acute leukemia.

In order to determine the nature of the cells in mitosis in acute leukemia, a parallel study was conducted by cytological and cytogenetic methods on the same marrow and blood samples. On direct marrow examination, erythrocyte precursors in mitosis are usually observed but ordinarily disappear following in vitro culture. In APL (M3) characterized by t(15;17) translocation, the comparison between the proportions of the different categories of cells in mitosis and of karyotypically normal and abnormal cells suggests that erythroblasts do not belong to the leukemic clone. An analogous situation is observed in AML (M2) with t(8;21) and in monocytic leukemia (M5) with chromosome abnormalities. Erythroleukemia could be divided into two categories, one with chromosome abnormalities and persistence of erythroblast mitoses after culture, and another with no detectable chromosome abnormality and with disappearance of erythroblast mitoses following culture. Other examples of blood malignancies demonstrate the importance of the method used in determining which cell categories belong to the leukemic clone. An interpretation of the results in terms of commitment 'level' of the involved stem cells and a distinction between 'primary' and 'secondary' chromosome abnormalities is proposed.

Acute Disease↗

t(15;17) in a promyelocytic form of chronic myeloid leukemia blastic crisis.

Two simultaneous translocations, t(15;17) and t(9;22), have been observed in a chronic myelogenous leukemia patient with acute promyelocytic blastic crisis. After remission obtention only karyotypes with t(9;22) were present. The occurrence of the two translocations in the same cell argues in favor of the specificity of t(15;17) versus acute promyelocytic differentiation.

Adult↗

Malignant and reactive erythroblasts in erythroleukemia (M6).

A cytogenetic and cytological study of 16 cases of erythroleukemia (M6) is reported. No chromosomal abnormalities were observed in 10 cases. Abnormalities were present in the other 6 cases, of which 4 were complex abnormalities. It was not possible to establish any correlation between the occurrence of morphologic abnormalities of the erythroid and megakaryocyte-platelet series and the presence of cytogenetic defects. Studies of mitoses by cytologic and cytogenetic methods concurrently performed in some cases suggest that two types of erythroleukemia can be distinguished: (1) cases with chromosomal abnormalities and a persistence of erythroblast mitoses in vitro (which suggests that the erythroblasts belong to the leukemic clone) and (2) cases with no chromosome abnormality and a disappearance of erythroblast mitoses after culture, suggesting that the erythroblasts are not members of the leukemic clone.

Adult↗

Does treatment with ARA-C in low dosage cause differentiation of leukemic cells?

A series of 21 patients (5 refractory anemias with an excess of blasts in transformation and 16 acute leukemias) were treated with small doses of ARA-C (10 mg/sq m/12 hr for 15-21 days). Improvement was noted in 15 cases (71%) and complete remission observed in 12 (57%). Complete remission was obtained after one course of treatment in 8 cases. The fact that these patients entered remission relatively slowly and did not suffer marrow aplasia suggests that low-dose ARA-C may function in vivo as it does in vitro, i.e., by inducing differentiation of leukemic blasts.

Acute Disease↗

[Prognostic value of chromosome anomalies in acute non-lymphoblastic leukemias].

The results of a cytogenetic study on 240 acute nonlymphocytic leukemia patients (187 adults and 53 children) were classified in NN (normal), AN (abnormal and normal) and AA (abnormal). Pronostic value of the classification was presented. A higher proportion of complete remission failures was observed in chromosomally abnormal patients (AN and AA). Survival of patients with complete remission was significantly shorter in AN and AA patients than in NN patients. An excess of constitutional chromosome abnormalities was observed in children.

Acute Disease↗

Acute monocytic leukemia chromosome studies.

Cytogenetic studies have been performed on 34 acute monocytic leukemia (M5) patients, 24 of the a type and 10 of the b type. No chromosomal abnormalities were found in 12 cases, in spite of the fact that the mitoses concerned monocytes. Different chromosomal aberrations were present in the other cases. In 12 of them, an abnormality of the chromosome 11 long arm was observed (mainly in the poorly differentiated type of M5), on bands q22-q24 in nine cases and on band q14 in three cases. The chromosome 11 long arm thus appears preferentially rearranged in M5 although this is not apparent in every case. Concomitant study of the mitoses with cytological and cytogenetic techniques suggests that erythroblasts may not be involved in the M5 leukemic process.

Adolescent↗

Unusual intracytoplasmic immunoglobulin inclusions in chronic lymphocytic leukaemia.

Unusual intracytoplasmic immunoglobulin inclusions were found by immunofluorescence in three patients with chronic lymphocytic leukaemia. The inclusions contained the same immunoglobulin chains as those detected on the plasma membrane, except for delta chains which were expressed on the cell surface and not in the cytoplasmic inclusions. The cytoplasmic staining persisted throughout culture for 8 or more days. An initial study of patients 1's cells showed that the inclusions contained only mu chains, and kappa chains gradually became apparent after in vitro culture. In a second study, the fresh lymphocytes contained both mu and and kappa chains. Initially, biosynthetic experiments showed production of mu chains which polymerized in the cytoplasm and were not secreted. Subsequently there was synthesis of heavy and light chains which assembled into monomeric subunits that were retained and secretion of free light chains. The apparent molecular weight of these immunoglobulin chains was larger than that of their secretory counterparts. Immunoelectronmicroscopy revealed cytoplasmic mu chains in strands of endoplasmic reticulum. In the two other patients, immunofluorescence displayed unusual staining patterns of bright networks in perinuclear areas.

Cytoplasm↗

Small doses of ARA-C in the treatment of acute myeloid leukaemia: differentiation of myeloid leukaemia cells?

Three patients with acute myeloid leukaemia were treated with small doses of ARA-C (10 mg/m2/12 h, subcutaneous injections) and complete remission was obtained. The small doses of ARA-C, the progressive evolution, the absence of aplasia before remission, the simultaneous presence of normal islets of promyelocytes and leukaemic myeloblasts, favour a differentiating role for the drug rather than an antimitotic effect.

Aged↗