Biomedical subjects

A Cork

Publications and source records attributed to A Cork.

89 records · Page 5Linked to original sources

PubMed1983

Philadelphia chromosome-positive adult acute leukemia with monosomy of chromosome number seven: a subgroup with poor response to therapy.

Thirty-four adult patients were seen at the University of Texas M. D. Anderson Hospital and Tumor Institute at Houston, Texas between 1969 and 1980 with acute leukemia (AL) and a deleted G-group chromosome that was shown by Giemsa banding to be a Philadelphia (Ph1) chromosome t(9;22) in 21 patients. Fourteen had the Ph1 chromosome as the sole abnormality, 12 had the Ph1 chromosome and loss of one chromosome of the C-group (identified by Giemsa banding analysis as number 7 in eight patients), while eight had the Ph1 chromosome and other changes. These three groups were similar in sex, age distribution and hematologic parameters. The median age of 40 was lower than usually seen in AL. The distribution of the morphologic subtypes was similar to that seen at this institution, with 50% being acute myeloblastic, 12% acute myelomonocytic, 20% lymphoblastic and 18% acute undifferentiated. The complete remission rate with chemotherapy was low: 25% in the Ph1 +/- 7, 50% in the Ph1 +/other group and 43% in the Ph1 +/other group. Median survival time was 8 months for the Ph1 +/- 7 group, 5.5 months for the Ph1 +/other group and 9.0 months for the Ph1 +/alone group. These patients with Ph1 + AL had higher white blood cell counts, increased extramedullary disease and poorer responses to therapy than usual for patients with AL. The deletion of chromosome 7 and the acquisition of the Ph1 chromosome identifies a group of patients with characteristics similar to all the patients with Ph1 + AL but a poor response to therapy and short remission duration.

Adolescent↗

PubMed1983

Chromosomal abnormalities in leukemia.

Since the discovery that human somatic cells contain 46 chromosomes, a number of diseases have been found to be related to abnormalities in chromosome structure or number. Many of these chromosome abnormalities are found in hematologic disorders, which have been called clinicocytogenetic syndromes. Cytogenetic studies in these disorders have proved to be helpful in both diagnosis and predicting response to therapy.

Acute Disease↗

PubMed1982

A comparative study of the effectiveness of different mitogens for karyotypic analysis in chronic B cell leukemia.

In order best to study the karyotypic abnormalities of nine patients with chronic lymphocytic leukemia of B cell origin, we used a combination of T and/or B cell mitogens so as to achieve an optimal proliferative response. As assessed by DNA synthesis, and subsequent cytogenetic study, pokeweed mitogen (PWM) and protein A Sepharose (PROT A) appeared to hold promise as potent stimulators of neoplastic B lymphocytes. Lipopolysaccharide from E. coli (LPS) proved to be an ineffective mitogen. Phytohemagglutinin (PHA), while producing the highest stimulation indices by DNA assay, appeared to induce predominantly diploid metaphases. Pseudodiploid clonal abnormalities were noted in three out of nine patients, while another four patients showed random structural abnormalities, including translocations, which were indicative of damage. Presence of the A33 antigen, as determined by HLA typing, was noted in five out of nine patients. The increased frequency of this antigen in patients with chronic B cell leukemia is discussed.

Adult↗

PubMed1981

Clinical implications of cytogenetic abnormalities in acute nonlymphocytic leukemia.

Banding techniques have been applied to the study of the karyotypic alterations associated with acute nonlymphocytic leukemia (ANLL). These studies have identified nonrandom changes which preferentially involve certain chromosomal elements. Correlation of these chromosomal aberrations with the clinical ahd hematological findings indicates the existence of clinicocytogenetic syndromes. These patients exhibit specific chromosomal alterations with a well-defined hematological picture and clinical behavior. In this article the clinical implications of the various types of specific chromosomal abnormalities seen in acute nonlymphocytic leukemia, as found in our laboratory and as reported in the literature, are reviewed and discussed.

Acute Disease↗

PubMed1980

Acute unclassified leukemia: A clinicopathologic study with diagnostic implications of electron microscopy.

By rigid cytological and cytochemical criteria, the diagnosis of acute and undifferentiated leukemia was established in 22 patients. According to defined criteria, the leukemic cells could not be classified by conventional light microscopic techniques employed in the study of hematopoietic tissue. Cytochemical studies including peroxidase, periodic acid schiff (PAS) and nonspecific esterase (alpha napthyl butyrate-reacting esterase) stains were done on fresh bone marrow samples, and the percentage of positive leukemia cells for each of these stains was determined on 200 cells. In this series of leukemias, cytochemistry at the light microscope level did not contribute to further classification. Subsequent electron microscopic examination of bone marrow samples from these patients confirmed the immaturity and nuclear/cytoplasmic asynchrony of the leukemic cells. Several in vivo neoplastic markers, such as nuclear blebs, increased nuclear bodies, and cytoplasmic fibrillar bundles could be demonstrated in these cells. Fourteen cases from this series exhibited peroxidase-positive developmental granule formation at the ultrastructural level and were reclassified as acute granulocyte leukemia (AGL). One case was reclassified as lymphoma (poor differentiated type), one case was diagnosed as acute monocytic leukemia (AmonoL), and six cases remained in the undifferentiated category (AUL). Clinical and laboratory features, response to treatment, and survival data were evaluated for these patients. This study demonstrated that electron microscopy is useful in the cytological diagnosis of human leukemia.

Acute Disease↗

PubMed1979

Hematologic and cytologic characterization of 8/21 translocation acute granulocytic leukemia.

Cytogenetic studies were performed in 546 patients with acute leukemia between 1968 and 1975. Two hundred thirty-four patients were aneuploid (42.9%), and 312 patients were diploid (57.1%). Among these, 32 patients were found to exhibit similar chromosomal alterations that appeared to involve specifically chromosomes 8 and 21. Banding studies in at least 15 of these patients confirmed the presence of a translocation between these two chromosomes. The cytogenetic findings were correlated with the hematologic and clinical data. It was found that each of these individuals had a typical picture of acute granulocytic leukemia with Auer rod-positive and peroxidase-positive cells. Ultrastructurally, the patients in this group also consistently demonstrated the presence of a nuclear bleb that has been positively associated with aneuploidy in acute leukemia. Clinically, they seemed to respond better to therapy than other adult patients with acute granulocytic leukemia. It is proposed that the 8/21 translocation acute leukemia represents a definite subgroup within the general category of acute granulocytic leukemia, with an incidence of approximately 7.3%.

Adolescent↗

PubMed1976

In vitro colony growth of acute myelogenous leukemia.

Bone Marrow↗

PubMed1976

In vitro colony growth of acute myelogenous leukemia.

Colony formation in vitro by marrow cells from patients with untreated acute myelogenous leukemia (AML) and from patients in AML relapse is infrequent using the standard Robinson assay. A newly developed culture system has been described in which marrow from AML patients in these disease stages form leukemic cell colonies. In this in vitro system, phytohaemagglutinin is the essential stimulator for colony formation. The leukemic origin of the colonies has been proven by ultrastructural morphology and cytogenetics. It appears that colony formation by leukemic cells in this system is predominantly independent from the leukocyte factor which is the main stimulator in the Robinson assay for growing colonies of marrow cells from haematologically normal individuals. Bone marrow cells in untreated acute myelogenous leukemia (AML) demonstrate abnormal growth in vitro in the Robinson assay (Robinson et al., 1971; and Bull et al., 1973). Characteristically, there is a near total failure of colony formation; predominantly clusters are formed containing 20 cells or less (Bull et al., 1973; Greenberg et al., 1971; Moore et al., 1973 and 1974, and van Bekkum et al., in press). The absence of colonies has been shown to be due to a marked decrease of the normal myeloid precursor cell population in untreated AML. The small agregate formation of AML cells has been attributed to the suboptimal response of leukemic cells to the leukocyte stimulation factor. Because this poor proliferation in vitro might not represent the maximal in vitro and in vivo proliferation potential of the leukemic cells, we studied a number of modifications of the in vitro culture system. A number of factors were studied which may have some influence on cell proliferation in general, notably phytohaemagglutinin (PHA), which induces lymphocyte colonies in vitro (Rozenszajn et al., 1974), and endotoxin which has been demonstrated to increase the labelling index of leukemic cells in vivo (Golde et al.). In this paper an in vitro system is described in which marrow cells from untreated AML and AML in relapse were stimulated by phytohaemagglutinin (PHA) to form leukemic cell colonies in soft agar. These (similar) cells predominantly formed small aggregates (20 cells or less) in the presence of the normal leukocyte feeder layer alone. Moreover, in the course of the experiments, it appeared that by adding low concentrations of endotoxin to the cultures, the stimulating effect of PHA could be amplified.

Bone Marrow↗

PubMed1974