Search PubMed⌕ Search

Biomedical subjects

F Carbonell

Publications and source records attributed to F Carbonell.

At least 73 records · Page 4Linked to original sources

bcr rearrangement and translocation of the c-abl oncogene in Philadelphia positive acute lymphoblastic leukemia.

The Philadelphia (Ph1) chromosome, the cytogenetic hallmark of chronic myeloid leukemia (CML), has also been detected in a significant number of acute lymphoblastic leukemias (ALL). Using in situ hybridization, we demonstrate that in accordance with observations in CML the Ph1 chromosome in ALL patients is the result of a consistent translocation of the c-abl oncogene to the Ph1 chromosome. Southern blot analysis using bcr probes, however, suggests that Ph1-positive ALL includes heterogeneous leukemic subtypes: six ALL patients showed bcr rearrangements as observed in CML; in three other patients recombination involving 5' bcr sequences could be demonstrated, but the corresponding translocated 3' bcr sequences were not detectable. A third group of five patients did not show any bcr rearrangements at all. Northern blot analysis using RNA from three Ph1-positive ALL patients revealed that in the leukemic cells of two patients larger c-abl mRNA transcripts were present, as in CML. In the RNA of one patient without a detectable bcr rearrangement, only the normal c-abl mRNA transcripts are present. The observed heterogeneity in bcr rearrangements of this group of Ph1-positive ALL patients is in contrast with the consistent results obtained in more than 50 Ph1-positive CML patients investigated in chronic and acute states.

Chromosome Deletion↗

Karyotypic evolution in patients with myelodysplastic syndromes.

Serial cytogenetic studies were performed in 33 patients with myelodysplastic syndrome in order to establish the frequency of karyotypic evolution and to correlate the chromosome and clinical findings during the course of the disease. Fifteen of the 33 patients (45%) showed abnormalities in the first cytogenetic study and this percentage increased to 57% during the course of the disease. A stable karyotype (normal or abnormal) was found in 19 patients (58%), whereas the rest (42%) showed an unstable karyotype. Trisomy 8, monosomy 7, and del5q were the most frequent abnormalities, not only at presentation, but also during karyotypic evolution. Seven patients (23%) with a known evolution proceeded to leukemia; four of them had stable (22%) and three unstable (25%) karyotypes; however, 33% of patients with unstable karyotypes and only 5% with stable karyotypes died from complications of the disease. Our results suggest that karyotypic evolution is relatively frequent in these patients; this evolution could be related to a poor clinical prognosis, either evolving to leukemia or death.

Acute Disease↗

Mixed megakaryocytic-granulocytic differentiation during diffusion chamber culture of peripheral blast cells from the blast crisis of chronic myelocytic leukemia.

Morphologically and cytochemically undifferentiated peripheral blast cells from three patients in blast crisis of Ph'-positive chronic myelocytic leukemia were analysed morphologically, immunologically and cytogenetically prior to and during in-vivo diffusion chamber culture (DC) to investigate their differentiation capacity. In two patients immunological markers characteristic of the megakaryocytic lineage were found on the original cells, but lineage-specific differentiation markers were absent on the blast cells of the third patient. During DC culture multilineage differentiation capacity could be demonstrated immunologically and morphologically in all three patients with expression of megakaryocytic and granulocytic markers as well as terminal differentiation along these lineages. Cytogenetic analysis prior to and during DC culture provided evidence that the cells differentiating in culture were derived from the blast crisis clones and that the event leading to blast crisis might have occurred in a pluripotent precursor cell which retained its differentiation capacity along several lineages.

Adult↗

Involvement of chromosome 9 in variant Ph1 translocation.

Cytogenetic analysis of a patient with chronic myelocytic leukemia revealed a translocation (21; 22) (q 22; q 11) without a detectable involvement of chromosome 9. By in-situ hybridization studies, however, we demonstrate a reciprocal translocation of sequences from chromosome 9 (c-abl) to Ph1 and chromosome 22 (bcr) to 9, respectively. These observations suggest a consistent participation of chromosome 9 in the Ph1 translocation, regardless of the cytogenetic subtype.

Chromosomes, Human, 6-12 and X↗

Allogeneic transplantation of blood stem cells concentrated by density gradients.

Discontinuous albumin density gradients were used to physically separate hemopoietic cells from immunocompetent lymphocytes in peripheral blood mononuclear cells of dogs. Transplantation of these stem cell concentrates into lethally irradiated allogeneic recipients restored hemopoiesis in nine of 12 animals. Tolerance and long-term survival, however, were achieved only in pairs matched for major histocompatibility antigens. These animals showed stable chimerism in bone marrow cells but transiently regenerated autochthonous cells demonstrable only in the peripheral blood. As compared with earlier studies using grafts of unseparated peripheral blood mononuclear cells, the numbers of CFUc transplanted were similar; the number of mononuclear cells, however, was reduced by a factor of 60. It thus appears that the granulocyte-macrophage colony-forming assay (GM-CFUc) is able to predict within limits the hemopoietic potential of a graft. Although very low numbers of blood-derived CFUc were effective (33,000-42,000/kg body weight), the superiority of blood stem cells over bone marrow grafts remains to be established.

Animals↗

Fetal liver transplantation in the dog. I. Restoration of hemopoiesis with cryopreserved fetal liver cells from DLA-identical siblings.

Fetal liver cells (FLC) were obtained from beagle fetuses 52 days postconception, and were cryopreserved prior to transplantation into ten sibling recipients that had previously been exposed to total-body irradiation delivered in 3 fractions of 6 Gy each at 4 days, 2 days, and 2 hr before grafting. Donors and hosts were genotypically identical for dog leukocyte antigens (DLA)-A, B, and D. A rapid and lasting engraftment was achieved in all animals following the transfer of 0.2 X 10(8) to 1.6 X 10(8) mononuclear FLC/kg body weight, which were equivalent to 0.9 X 10(4) to 19.8 X 10(4) granulocyte/macrophage progenitor cells (CFU-GM)/kg. Between days 14 and 20 posttransplant pretreatment levels were detected for blood granulocytes, between days 23 and 28 for circulating platelets, and between days 35 and 40 for the erythrocyte count and hemoglobin concentration. Increasing the number of CFU-GM transfused resulted in an accelerated granulocyte and platelet recovery. Bone marrow cells were of donor origin throughout the observation interval, but declining proportions of host lymphocytes circulated in the peripheral blood during the initial recovery phase. In two dogs, skin alterations that might indicate slight graft-versus-host disease (GVHD) were noted following days 20 and 70, respectively. Six recipients had to be sacrificed due to inanition, probably secondary to radiation-induced pancreatic insufficiency two to three months after grafting. The results of this study indicate that cryopreserved FLC are highly effective in restoring hemopoiesis in DLA-compatible sibling dogs. Transplantation of canine FLC may prove valuable in analyzing mechanisms pathogenetically related to graft rejection or to the development of GVHD following the transfer of T-cell-depleted hemopoietic grafts at a preclinical stage.

Animals↗

Hemopoiesis and immune functions in dogs following fetal liver transplantation.

Ten beagles were exposed to total body X-irradiation (3 X 6 Gy) and rescued with cryopreserved fetal liver cells from DLA-identical siblings obtained around the 52nd day of gestation. Grafts contained 0.2-1.6 X 10(8) mononuclear cells/kg and 0.9-19.8 X 10(4) granulocyte-macrophage progenitor cells/kg. Hemopoiesis and immune functions were followed for up to one year after fetal liver transplantation (FLT). There was a prompt engraftment in all recipients. Bone marrow metaphases were always of donor origin, whereas some host lymphocytes circulated for 2-3 months. Blood granulocytes and monocytes rose to pre-treatment levels within 2-3 weeks of FLT and platelets and erythrocytes were normal within 3-4 and 5-6 weeks, respectively. The relative incidence of bone marrow CFU-GM was normal by day 14 and the absolute numbers of circulating CFU-GM remained elevated for one year after day 14. Blood lymphocytes reached control numbers between days 35 and 101 with a faster B cell than T cell recovery. Their response to mitogen stimulation was normal by day 75, while the mixed lymphocyte reaction tended to be reduced for one year. Serum levels of IgM (day 35) and IgG (day 49) recovered earlier than IgA levels (day 270). Thus, cryopreserved canine fetal liver cells can restore hemopoiesis and immunocompetence with considerable rapidity in histocompatible, adult siblings pre-treated with total body irradiation, and, since they lack mature T cells, may be used to analyze effector mechanisms that mediate rejection of T cell-depleted allografts under less favourable conditions.

Animals↗

Growth and cytogenetic characteristics of bone marrow colonies from patients with 5q-syndrome.

Early erythroid precursor cells and myeloid progenitor cells (CFU-GM) from four patients with 5q-syndrome were cultured in order to study the in vitro growth patterns and to determine the clonal origin of this hematologic disorder. Cultures of CFU-GM exhibited normal colony growth, while erythroid progenitor cells demonstrated a marked decrease or absence of colony growth. Chromosomal studies indicate the 5q-chromosome is present in both hematopoietic progenitor cells, suggesting that the syndrome is an acquired clonal disease arising from a pluripotent hematopoietic stem cell. Follow-up cytogenetic studies reveal a decrease in the number of normal metaphases. This finding is consistent with reports that emphasize the slowly progressive nature of this malignant stem cell defect.

Aged↗

[Biologic reagents].

Explore the source record for details and available documents.

ABO Blood-Group System↗

[Bone marrow transplantation in panmyelopathy, acute leukemia and chronic myelocytic leukemia: results of the Ulm Transplantation Group].

From 1972-1983 53 patients underwent bone marrow transplantation. The median age was 18 years (3-41). 27 patients suffered from severe aplastic anaemia, 22 patients had acute leukaemia and 4 patients had chronic granulocytic leukaemia in chronic phase. Out of 22 patients with acute leukaemia, 2 had florid leukaemia, 2 had an early relapse and 18 patients were in first or second remission of their disease. 2/53 patients received a syngeneic transplant, 51/53 patients an allogeneic transplant. 47/51 patients had a HLA-A, B, C-identical, MLC-negative sibling donor, 1/51 had a HLA-A, B-C-identical, MLC-positive sibling donor, 2/51 a HLA-phaenotypical identical parental donor and 1/51 a HLA-identical, MLC-negative unrelated donor. The comparison of the results obtained in patients with severe aplastic anaemia transplanted from 1972-1979 with those transplanted from 1980-1983 shows that the bone marrow transplantation has to be performed in an early stage of the disease before the patients become multiple transfused, sensitized and severely infected and that the conditioning regimen for polytransfused patients has to be more intensive than in untransfused patients. From the patient group transplanted 1972-1979, only 1/14 patients is a long-term survivor in contrast to 8/13 patients transplanted from 1980-1983. 11/22 patients with acute leukaemia are alive between more than 5 years and 14 days after bone marrow transplantation. Only 1/4 patients, who were transplanted not in remission, is alive.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Cytogenetic studies in dogs after total body irradiation and allogeneic transfusion with cryopreserved blood mononuclear cells: observations in long-term chimeras.

Cytogenetic studies were performed on two dog groups after total body irradiation and allogeneic transfusion with cryopreserved blood mononuclear cells. The first group of dogs was transfused with unseparated leukocytes and suffered from graft-versus-host disease (GvHD). Cytogenetic studies demonstrated only cells of donor origin in all dogs of this group. The second group of animals was transfused with fraction 2 of a discontinuous albumin gradient. The dogs of this group did not develop GvHD, and the cytogenetic studies showed the presence of a mosaic of cells from donor and recipient origin in all of them. These results suggest that the GvHD may suppress autochthonous regeneration.

Animals↗