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Biomedical subjects

M T Daniel

Publications and source records attributed to M T Daniel.

At least 91 records · Page 5Linked to original sources

Cytogenetic studies on 519 consecutive de novo acute nonlymphocytic leukemias.

Cytogenetic studies were performed in the same laboratory on 519 untreated cases of de novo acute nonlymphocytic leukemia (ANLL) between 1977 and 1985. The overall incidence of clonal chromosome abnormalities was 54.3%; higher in children (67.5%) than in adults (50.4%). The distribution of chromosome abnormalities was uneven, according to the categories of the FAB nomenclature. The highest frequency of chromosome changes was observed in ANLL-M3 and the lowest in M1 and M6. The frequency of specific chromosome abnormalities and of their associated changes were also estimated. Monosomy 7 was detected in three patients with acute megakaryocytic leukemia (M7). Six cases with two abnormal chromosomally unrelated clones were observed and six constitutional chromosome abnormalities were detected. A clearer knowledge of the incidence of various chromosomal changes in ANLL seems necessary for better differentiation between the so-called primary and secondary chromosome abnormalities and for prognostic evaluation.

Acute Disease↗

Prognostic significance of chromosomal abnormalities in acute nonlymphocytic leukemia: a study of 343 patients.

Clonal chromosome abnormalities of 343 patients with de novo acute nonlymphocytic leukemia (ANLL) have been tentatively correlated with prognosis. All the patients were treated according to therapeutic protocols in the same hospital. The complete remission rate and median survival were generally lower in AA-ANLL (ANLL with only karyotypically abnormal metaphases) when compared with NN- and AN-ANLL. Similarly, AA-ANLL had the poorest prognosis in the majority of the classes of the French-American-British nomenclature. ANLL with inversion and/or deletion of chromosome #16 had the best prognosis, and ANLL with t(8;21) was not particularly favorable, nor was acute promyelocytic leukemia with t(15;17). ANLL with complex chromosomal abnormalities had the poorest prognosis. The conclusion is that chromosomal aberrations do have a prognostic significance in ANLL, but that this significance is dependent on the types of chromosomal aberrations.

Acute Disease↗

T cell-derived blast crisis in chronic myelocytic leukemia.

We describe herein the occurrence of a T cell-derived blast crisis of chronic myelocytic leukemia which presented as a typical T cell leukemia on clinical (thymic mass and high white blood cells) and immunological grounds (T6+ T4+ T8+), with rearranged T cell receptor genes and germ line immunoglobulin genes. A Philadelphia chromosome was detected in all blast cell mitoses. The significance of T cell involvement during the chronic and acute phases of chronic myelocytic leukemia is discussed.

Adult↗

[Improved results in the treatment of acute monoblastic leukemia: analysis of 91 patients treated in the 01 AM 81 protocol].

A total of 91 patients with acute monoblastic leukemia (AML) were treated following two induction regimens (ARA-C + RBZ, with of without CPA), and a unique maintenance therapy (CNS prophylaxis and reinductions every 6 weeks, for 36 months). Complete remission (CR) was obtained in 84% of patients. The only prognostic factor significantly influencing the CR rate was age, with 92% for the less than 40 years group and 75% for the greater than or equal to 40 years group. CR was not influenced by sex, tumoral syndrome, leukocytosis, cytological subclassification (M5A, M5B), or induction regimen with or without CPA. The duration of CR in these forms which have a traditionally poor prognosis, was no different from other forms of AML (21 months), and the disease-free survival at 50 months was 45%. These results, pertaining to the largest published series treated by the same protocol, are the best reported in literature and confirm the role of induction and maintenance therapy in CR.

Adult↗

[Acute myelomonocytic leukemia with abnormal eosinophils].

A total of 32 patients with acute myelomonocytic leukemia and abnormal bone marrow eosinophils (LAM4 Eo) have been treated at this Institute since 1977. Abnormalities of chromosome 16 have been noted in 14 of 22 evaluable cases. After a median follow-up of 4 years, median duration of complete remission was 46 months and median duration of survival had not been reached; 8 patients have been receiving no therapy for between 1 and 6 years. These results compare favorably with LAM4 without abnormal bone marrow eosinophils (median duration of complete remission: 12 months; median duration of survival: 14 months). LAM4 Eo constitute a particular entity, with a special hematological presentation, the incidence of abnormalities of chromosome 16, and a particularly good prognosis.

Adolescent↗

A t(8;14)(q24;q11) translocation in a T-cell leukemia (L1-ALL) with c-myc and TcR-alpha chain locus rearrangements.

Cell lines established from T-cell leukemias have recently been reported to exhibit a chromosome translocation t(8;14) involving proto-oncogene c-myc and the gene of the T-cell receptor alpha-chain(TcR-alpha). In this work, we have studied a case of T-cell leukemia presenting a t(8;14)(q24;q11) translocation that was found in fresh leukemic cells taken during relapse, but was absent in cells collected at diagnosis. Hybridization analysis showed that the breakpoint on chromosome 8 was located 3' to the c-myc exon 3. A TcR-alpha-specific original probe (D14S7, Mathieu-Mahul et al., 1985) revealed two differently rearranged patterns in DNA from leukemic cells obtained at diagnosis and during relapse. In contrast, the rearranged TcR-beta-gene DNA pattern did not change during the course of the disease, indicating that leukemic cells were clonally related. These data indicate that the chromosome breakpoint in 14q11 is situated in the TcR-alpha locus. These results suggest that translocations t(8;14) involving TcR-alpha and c-myc genes in T-cell malignancies are analogous to variant t(2;8) and t(8;22) translocations observed in Burkitt lymphoma. They also establish that the same types of molecular rearrangements due to a t(8;14)(q24;q11) translocation, at first described in T-cell lines established in culture, also exist in vivo and may play a role in the evolution of the leukemic process.

Child↗

Abnormalities of the short arm of chromosome 12 in acute nonlymphocytic leukemia and dysmyelopoietic syndrome.

Abnormalities of the short arm of chromosome #12 (12p) were found in 18 patients, 7 with previously untreated acute nonlymphocytic leukemia (ANLL) and 11 with dysmyelopoietic syndromes (MDS) or ANLL following treatment for another malignant disease. The chromosome #12 abnormality was a partial deletion in 15 patients and a translocation in 3. The 12p- was the sole chromosomal abnormality in seven patients (four with de novo ANLL) and was associated with other chromosome abnormalities in eight patients. Thus, partial monosomy for 12p was often associated with other chromosomal changes and was a secondary abnormality in some cases. The consequences of this hemizygosity for genes located at 12p are discussed with references to the possible expression of a potentially mutated recessive gene. The study of c-K-ras 2, normally located at 12p, must be done in such cases, as the association of secondary blood disorders and multiple chromosome abnormalities suggests a possible mutation of this c-oncogene on chromosome #12.

Acute Disease↗

Can peripheral T-cell lymphomas be morphologically subclassified? A morphometric approach to 21 cases.

Morphometric analysis of nuclear sizes and shapes was carried out on semithin sections of lymph node for 21 patients suffering from non-Hodgkin's peripheral T-cell malignant lymphoma (ML) (excluding mycosis and Sézary syndrome). Twenty cases of B-cell ML and three cases of Sézary syndrome with massive lymph node infiltration were also studied as references. Wright and Isaacson's recent proposals were applied to classify the peripheral T-cell MLs into monomorphic medium-cell ML (eight cases), pleomorphic ML (nine cases), and monomorphic large-cell ML (four cases). These three classes were readily distinguishable by morphometric analysis of nuclear sizes. Nuclear areas and their coefficients of variation were higher in pleomorphic MLs than in monomorphic medium-cell MLs (p less than 0.01). Large-cell monomorphic MLs were set apart by the histograms of their nuclear sizes. The mitoses were evaluated on histological sections and found to be more numerous in pleomorphic ML than in monomorphic medium-cell ML (p less than 0.05). Nuclear irregularity in the 21 cases of peripheral T-cell ML was lower than in Sézary cells. Morphometry clearly demonstrates the morphological distinctiveness of the subclasses of peripheral T-cell ML. Their biological significance has yet to be determined.

Adult↗

Immunological typing of acute lymphoblastic leukemia: concurrent analysis by flow cytofluorometry and immunocytology.

For 60 cases of acute lymphoblastic leukemia (ALL) immunological typing was done concurrently by the avidin-biotin-peroxidase method using cytocentrifuged smears and by flow cytofluorometry for the study of surface antigens. The use of a large panel of antibodies detecting differentiation antigens allowed us to sub-classify 57/60 cases as 43 B-lineage ALLs and 14 T-lineage ALLs. The two types of ALL can be accurately distinguished by the expression of the antigens recognized by the antibodies of the clusters of differentiation CD19 (B4) and CD7 (Leu 9). Almost perfect agreement was obtained between the results of the two methods for antigens DR, CD10 (cALLA;J5) and CD7. A number of discordances were observed with other antigens [CD19 (B4), CD20 (B1), CD22 (To15), CD1 (T6), CD2 (T11), CD4 (T4), CD8 (T8), CD3 (T3), T9, T10]. In spite of these discordances, the avidin-biotin-peroxidase method can predict the lineage involved in most ALLs with a high degree of reliability. Nevertheless, for weakly expressed surface antigens (such as B4 and B1) the immunocytological method is less sensitive than flow cytofluorometry and can only approximately determine the stage of differentiation of neoplastic cells. Furthermore, the existence of cases which are at the same time negative with flow cytofluorometry and positive with immunocytology is consistent with the intracytoplasmic expression of certain differentiation antigens. Thus in the course of lymphoid differentiation, intra-cytoplasmic expression of T3, To15 and possibly J5 precedes their expression at the cell surface.

Antigens, Surface↗

[Translocation t(1; 14) and rearrangement of the gene for the alpha chain of the T-cell receptor in acute T-lymphoblastic leukemia].

A t(1; 14) (p32; q11) translocation has been found by the cytogenetic study of a T cell acute lymphoblastic leukemia patient. Molecular hybridization with a probe (D14S7) which recognizes a fragment of the alpha chain T receptor gene has shown a rearranged EcoRI 11.0 kb band in addition to the germline 3 and 8 kb bands. This translocation infrequently described until now is a new example of an alpha chain gene rearrangement in T cell malignancy. Moreover the breakpoint on chromosome 1 may also involve the newly isolated protooncogene, L-myc, normally localized on the chromosomal band 1 p32.

Adolescent↗

[Monoblastic (M5a) form of relapse in acute myeloblastic (M2) leukemia with t(8;21)].

An exceptional case of acute myeloblastic leukemia (M2) with t(8;21) relapsed as an acute monoblastic leukemia (M5). At that time only a minority of metaphases exhibited a t(8;21) and/or abnormality of chromosome No 11 long arm whereas various other chromosomal changes were present. The existence of a relapse of M2 with t(8;21) as M5 is discussed in relation to the commitment of the cells which became leukemic, and to the possibility of a second leukemia.

Child↗

Low-dose cytosine arabinoside treatment for acute nonlymphocytic leukemia in elderly patients.

Thirty patients older than 65 years of age with acute nonlymphocytic leukemia were treated with low-dose cytosine arabinoside (10 mg/m2 subcutaneously every 12 hours for 15 to 21 days). Fifteen achieved complete remission and five had partial remission. Treatment was more effective when initial bone marrow cellularity was low (P = 0.007). Four of six patients with secondary leukemia entered complete or partial remission. Therapy was well tolerated with reduced myelosuppression and few number of early deaths. Sixteen patients followed the whole treatment as outpatients. Six of 12 patients who achieved complete remission showed no evidence of post-therapeutic bone marrow aplasia. These data are consistent with the view that low-dose cytosine arabinoside acts on leukemic cells as a differentiating agent.

Acute Disease↗

Two Burkitt's lymphomas with chromosome 6 long arm deletions.

Two new European Burkitt's lymphoma (BL) cases are reported. Their karyotypic abnormalities were unusual, without involvement of chromosomes #8, #14, #2, or #22. However, in both tumors, a 6q- chromosome was, present. These findings raise questions about the definition of BL and the involvement of various different DNA sequences in the mechanisms of BL genesis.

Adult↗