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Biomedical subjects

M Sessarego

Publications and source records attributed to M Sessarego.

At least 109 records · Page 6Linked to original sources

Bone marrow transplantation for chronic granulocytic leukemia.

Thirty patients with chronic granulocytic leukemia (CGL), were given cyclophosphamide 60 mg/kg on each of 2 consecutive days, followed by total body irradiation (TBI) 10 Gy and an HLA-identical bone marrow transplant (BMT). Eleven patients were in the accelerated phase of their disease (CGLacc) or in second/secondary chronic phase (CGL-2CP), with a median age of 33 years: four patients died of transplant related complications, and four of recurrent leukemia; three patients are alive and well 19, 31, 33 months from BMT. The actuarial 33-month survival is 27%. The actuarial relapse rate is 50%. Nineteen patients were in their first chronic phase (1CP), with a median age of 32 years: three died of graft versus host disease (GvHD), two of infection, and two of acute respiratory distress syndrome (ARDS); 12 are alive and well 6 to 29 months post-BMT. The actuarial 29-month survival is 63%. The actuarial survival of patients younger than 30 years is 63%, compared to 62% for patients older than 30 (P = 0.1). The survival of patients grafted within or after 24 months from the onset of CGL is respectively 87% and 45% (P = 0.04). None of the patients grafted in 1CP had a true hematologic-cytogenetic relapse. The Ph' chromosome was detected on one occasion in two patients 12, 13 months post-BMT: they both remain hematologically normal and Ph1-negative 3 to 6 months later, after discontinuation of cyclosporin A. This study confirms that survival exceeding 60% can be obtained in CGL in the first chronic phase, whereas less than 30% of patients will survive if grafted in accelerated, second/secondary chronic phase, mainly because of leukemic relapse. The duration of the disease seems to be relevant to the outcome of the transplant. The effect of post-transplant immunosuppression, in our case cyclosporin A, on the interaction between normal and Ph1-positive hemopoietic cells, may deserve further attention.

Adolescent↗

Acute myelogenous leukemia with translocation t(8;21): a cytogenetic study of seven cases.

Seven cases of acute nonlymphoblastic leukemia showing t(8;21)(q22;q22) at diagnosis are described. Involvement of a sex chromosome was found in all patients (in six cases as a loss, and in one as a Y duplication), thus, confirming the suggestion of a correlation between these two chromosomal abnormalities. The constitutional folic acid-sensitive fragile site fra(8)(q22) was not detected, in spite of careful analysis of over 300 metaphases of cells grown in folic acid-free medium. Morphologic diagnoses and clinical aspects are briefly discussed.

Adult↗

Involvement of chromosomal region 9q34 in a case of variant Ph1 translocation t(22;22).

In a patient with chronic myelocytic leukemia chromosome analysis showed a translocation (22;22) (q13;q11). Chromosomes 9 were apparently not involved. Using somatic cell hybrids and a v-abl probe, we demonstrated the translocation of c-abl sequences from chromosome 9 to chromosome 22q-. This confirms the hypothesis that the translocation of c-abl oncogene is essential for the development of Ph1 positive CML.

Chromosome Banding↗

Competitive survival/proliferation of normal and Ph1-positive haemopoietic cells.

Bone marrow (BM) cells from 10 patients with Ph1-positive chronic granulocytic leukaemia (CGL) were placed in long-term cultures in the presence of fetal calf serum (FCS) and horse serum (HoS), or in the presence of human AB serum. The long-term cultures were started with three different cell combinations: (1) CGL BM cells (four cases), (2) CGL BM cells + normal BM cells (1:1 ratio) from an HLA identical sex-matched sibling (five cases), (3) CGL BM cells + normal BM cells (1:1 ratio) from an HLA identical sex mismatched sibling (five cases). Cytogenetic studies were performed at weeks 0, 3, 4 and 5 of culture. The results of this study can be summarized as follows: (a) Ph1-positive cells could be detected at any time of culture in all three of the described cell combinations; (b) a population of Ph1-negative cells of patient origin could be detected after 3-5 weeks of culture; (c) there was a trend for a better survival of Ph1-negative cells in cultures supplemented with FCS + HoS and, conversely, of Ph1-positive cells in cultures containing human serum. These results warrant further studies on the possibility of manipulating survival and proliferation of normal and leukaemic cells by varying the culture conditions.

Bone Marrow↗

Unusual Ph translocations in CML: four new cases.

Four variants of the Ph chromosome translocation in chronic myelogenous leukemia (CML) patients are described. Two had an unusual simple translocation involving chromosomes #7 and #17. In two cases, the translocation, aside from involving #9 and #22, involved a third chromosome, chromosome #6 and chromosome #11, respectively. Three cases showed also karyotypic evolution during the blastic phase of the disease: in two cases, a new reciprocal translocation was found that involved a chromosome #9 at band q34. The clinical and cytogenetic significance of these results is briefly discussed.

Adolescent↗

Effect of endothelial cell conditioned medium on the growth of human bone marrow fibroblasts.

Both endothelial cells (EC) and fibroblasts, two discrete populations of hemopoietic stroma, are known to modulate the proliferation and differentiation of hemopoietic progenitors. Recent reports also demonstrated that EC stimulate the in vitro growth of fibroblasts via a soluble factor. This finding seems to support the hypothesis that EC may play a role in the pathogenesis of bone marrow fibrosis in myeloproliferative disorders (MD). We have studied the effects of the conditioned medium (CM) from human umbilical vein EC cultures, obtained in serum free conditions, on the growth of bone marrow fibroblasts from normal donors and from patients with MD. The results show that EC derived CM contains a factor which stimulates the proliferation of fibroblasts and that can act as an authentic growth factor by inducing "quiescent" fibroblasts to proliferate. Moreover, we found that this endothelial derived growth factor (EDGF) equally promotes the proliferation of both normal and pathological progenitors of bone marrow fibroblasts (CFU-F) by increasing both the number and the size of the colonies.

Bone Marrow Cells↗

Demonstration of phosphoglucomutase 1 in a subclone of the K-562 cell line.

Phosphoglucomutase 1, an enzyme mapping on the short arms of chromosome 1, is constantly missing in the leukemic cell line K-562 in spite of the presence of three No. 1 chromosomes. In the present work, a subclone of the cell line, K-562 (S)P, is described, where the enzyme can be demonstrated, thus excluding a small deletion as the cause for the lack of expression of phosphoglucomutase 1. The relationship between the presence of the enzyme and the karyotype changes in this subclone is analyzed. Addition of several inducers to the standard K-562 line failed to elicit expression of the enzyme.

Cell Line↗

Regulation of acetylcholinesterase expression in the K-562 cell line.

Acetylcholinesterase, an erythroid marker constitutively expressed in K-562 cells, can be further induced by sodium butyrate. The highest level of acetylcholinesterase induction is reached in approximately equal to 3 days, in parallel with increased hemoglobin expression. Acetylcholinesterase induction is reversible, and repeated addition of butyrate is necessary to maintain a high level of the enzyme. Actinomycin D inhibits the induction.

Acetylcholinesterase↗

Clonal origin of cells restricted to monocytic differentiation in acute nonlymphocytic leukemia.

Two patients with acute monocytic leukemia and heterozygous for the Mediterranean variant of the X-linked enzyme, glucose-6-phosphate dehydrogenase (G6PD), were investigated to determine the number and type of progenitor cells involved. Mosaicism for Mediterranean G6PD was assessed by the different rate of utilization of 2-deoxy glucose-6-phosphate (2dG6P) by normal and Mediterranean variants of G6PD. The monocytoid blasts were found to express one type of G6PD only, indicating their clonal origin from a common progenitor cell, whereas all other hemopoietic cell populations tested expressed the heterozygous phenotype. The finding of a unique involvement of the monocytic line in two cases of acute nonlymphocytic leukemia (ANLL) represents further evidence of heterogeneity of stem cell involvement in ANLL.

Cell Differentiation↗

Coincidence between fragile site expression and interstitial deletion of chromosome 11 in a case of myelofibrosis.

Cytogenetic examination of multiple peripheral blood cultures of a patient with myelofibrosis with myeloid metaplasia revealed the presence of an interstitial deletion of the long arm of chromosome 11, del(11)(q13q21). A folic acid dependent fragile site fra(11)(q13) was found in about 12% of the cells. The possible correlation between constitutional fragile site and acquired chromosomal alteration is discussed briefly.

Chromosome Deletion↗

Masked Philadelphia chromosome caused by translocation (9;11;22).

In a patient with chronic myelocytic leukemia (CML), chromosome analysis revealed a translocation involving chromosomes No. 9, 11, and 22, with three break points, thus giving origin to a so-called "masked" Philadelphia chromosome (Ph1). A review of similar cases reported in the literature indicates that a masked Ph1 is very rare, that the chromosomes involved vary from case to case, and that in most cases the pattern of the rearrangement is quite different from that of two- and three-chromosome variant Ph1 translocations.

Chromosomes, Human, 21-22 and Y↗

Fibroblastoid colony-forming cells in myeloproliferative disorders.

The properties of human bone marrow fibroblastoid colonies (CFU-F) were studied in normal subjects and in patients with myeloproliferative disorders. Colony incidence was within normal values in all groups of patients analyzed except for myelodisplastic syndromes, with higher mean value. The growth rate of CFU-F is inversely related to the initial colony-forming efficiency both in normal subjects and in patients. Direct correlation between CFU-F and granulocyte-macrophage colony-forming unit (GM-CFU) was detected only in normal subjects, but lacked in patients. Higher number of CFU-F was observed in subjects with increased incidence of bone marrow megakaryocytes or peripheral blood platelets, irrespective of the underlying disorders and the platelet-derived growth-factorenhanced cloning efficiency of bone marrow fibroblasts.

Blood Platelets↗

Expression of erythroid acetylcholinesterase in the K-562 leukemia cell line.

Differentiation-dependent expression of enzyme loci was evaluated in two human leukemic cell lines, the pluripotent leukemia cell line K-562 and the promyelocytic-like cell line HL-60. Acetylcholinesterase, a marker of erythroid differentiation, was present in K-562 cells and absent in HL-60 cells. This difference between the two lines was apparently unrelated to dosage effect; other enzymes carried on trisomic chromosomes in K-562 cells did not show dosage effect. Acetylcholinesterase activity was higher in subclone K-562 (S), which shows higher expression of hemoglobin. Electrophoretic mobility of acetylcholinesterase from K-562 (S) was of fetal type.

Acetylcholinesterase↗

Marked karyotype abnormalities in two cases of acute myelogenous leukemia.

Two patients with acute myelogenous leukemia with severe chromosome abnormalities are described. The cytogenetic analysis shows the following karyotype: patient No. 1: 41,XY,-1,-2,-4,-5,-13,-15,-17,-18,-22,+5 markers; patient No. 2: 46,XY,-2,-5,-7,-13,+16,-21,-21,+5 markers. In each patient one set of double minute chromosomes was observed.

Aged↗

Karyotype evolution in a case of chronic myelogenous leukemia with an unusual Philadelphia chromosome translocation, t(4;22), and an additional translocation, t(3;5).

A patient with chronic myelogenous leukemia was found, at the time of diagnosis, to have an unusual Philadelphia chromosome translocation, t(4;22) (q35;q11) and an additional previously unreported translocation, t(3;5) (q27;q22). The blastic crisis, which occurred after 14 months, was characterized by the appearance of i(17q). Ten months later, two different hyperdiploid cell lines with 50 chromosomes were found in about 20% of the metaphases examined.

Chromosome Banding↗

Urinary colony-stimulating factor in acute leukemia follow-up and correlation with various phases of the disease.

Urinary colony-stimulating factor (CSF) was assayed in 19 patients with various leukemias and was monitored in various phases of acute leukemia in 3 patients. Significantly higher CSF levels were found at the onset of leukemia with a monoblastic component. Continuous monitoring of CSF in a patient with acute myelomonocytic leukemia revealed a decrease in CSF level during the remission phase, followed by a rebound to high levels preceding the clinical and hematological relapse. Concomitantly, a colony-inhibitory factor (CIF) was detected. Both CSF and CIF of this patient were isolated and partially characterized.

Acute Disease↗