Philadelphia chromosome negative CGL.
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Chromosomes, Human, Pair 22↗
Biomedical subjects
P H Fitzgerald
Publications and source records attributed to P H Fitzgerald.
Ph-negative chronic myeloid leukaemia.
An analysis of five patients with Philadelphia chromosome (Ph) negative chronic myeloid leukaemia (CML) revealed that two were clinically and haematologically identical to Ph-positive CML whereas three should be reclassified as chronic myelomonocytic leukaemia (CMML). At a molecular level the first two patients showed the same juxtaposition of c-abl and bcr genes as is seen in Ph-positive CML. These genomic changes were not seen in the other three patients. Observations on these five patients suggest that the clinical course and prognosis of the rare patient who carries the Ph 'molecular defect' but lacks the Philadelphia chromosome is no different from Ph-positive CML.
Adult↗
A monoclonal antibody reacting with human basophils.
Bsp-1 is an IgM murine monoclonal antibody raised against the human erythroblastic leukemia cell line (HEL) that reacts with basophils but not neutrophils or eosinophils. Western blotting techniques showed that Bsp-1 reacts with a 45-kilodalton surface antigen on HEL cells. The distribution of Bsp-1 antigen on leukemic cells is confined to a basophilic leukemia cell line, KU812, chronic myeloid leukemia with basophilia, and some cases of acute undifferentiated leukemia. Bsp-1 might therefore be a useful reagent for the study of basophil function and differentiation.
Antibodies, Monoclonal↗
B cell lymphoma presenting as carcinoma of the lung.
A patient presented with superior vena caval obstruction caused by a tumour which resembled carcinoma of the lung both clinically and histologically. However, immunologic and cytogenetic analyses carried out on the mediastinal biopsy and on pleural fluid revealed that the tumour was of B cell origin, Burkitt-like in sub-type, and had the t(8;14) translocation. The nature of many poorly differentiated tumours may be more clearly identified with the help of immunological and cytogenetic analyses.
Antigens, Neoplasm↗
Evidence for the repeated primary non-disjunction of chromosome 21 as a result of premature centromere division (PCD).
A clinically normal 28-year-old woman had three conceptuses with trisomy 21 and one normal child. She showed minimal cytogenetic evidence of mosaicism: 4% of her blood cells and 6% of skin fibroblasts had trisomy 21. Also, 7% of her blood cells showed aneuploidy of the X chromosome which was associated with premature centromere division (PCD,X); 6% of fibroblasts showed trisomy 18, 10% of fibroblasts showed PCD,21, and 1% PCD,18. It is unlikely that this woman is a constitutional mosaic for trisomies X, 18, and 21, all at low levels. We suggest that she has a predisposition to irregular centromere separation and that chromosomes X, 18, and 21 are most susceptible to its action.
Adult↗
An evaluation of high resolution chromosome banding of hematologic cells by methotrexate synchronization and thymidine release.
Methotrexate-thymidine synchronization increased mitotic yield and the numbers of cells with longer chromosomes when compared with direct and day culture (24 hr) techniques. The longer chromosomes overlapped more than shorter ones, but this adverse effect of cell synchronization was outweighed by the substantial gains from increased band number of metaphase cells. A critical feature of the synchronization technique that determines chromosome length is the period of cell culture following thymidine release. This will depend on cell cycle time. Variable results obtained with the synchronization technique probably occur because the cell cycle time of leukemic cells differs from that of normal hematologic cells and normal lymphocytes. It may also differ between patients and between acute and chronic forms of leukemia.
Acute Disease↗
Leukaemia/lymphoma incidence in New Zealand: acute leukaemia subtypes in the South Island of New Zealand, 1983-1984.
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Acute Disease↗
Does multisomy of chromosome 1q confer a proliferative advantage in B-cell acute lymphoblastic leukemia?
Two patients fulfilled the clinical and hematologic criteria for B-cell acute lymphoblastic leukemia: the malignant cells had L3 morphology, bore B-cell markers, and carried the specific t(8;14) translocation. The leukemic cells of one patient were tetrasomic for 1q, and those of the other patient showed several separate cell lines with complete or partial trisomy of 1q. In the latter patient it appeared that a break close to the heterochromatin of 1q produced an unstable chromosome end which formed associations with the telomeres of at least seven other chromosomes. It is suggested that multisomy of 1q gives tumor cells a proliferative advantage and is secondary to the basic neoplastic event.
Adolescent↗
Host origin of in vitro bone marrow fibroblasts after marrow transplantation in man.
Two female patients who received bone marrow transplants from male donors showed the donor karyotype in all blood cells cultured with phytohemagglutinin and in all cells of bone marrow aspirate after direct or 24-hour culture preparation for cytogenetic study. The donor origin of myeloid cells was demonstrated specifically by identifying the male karyotype in the dividing cells of granulocyte/macrophage colonies in soft agar. Only the host female karyotype was found in fibroblast cell populations from cultured bone marrow aspirate. Bone marrow aspirate from transplant patients contained cells of host origin and cells of donor origin; both will proliferate in culture.
Anemia, Aplastic↗
Telomeric association of chromosomes in B-cell lymphoid leukemia.
About 20% of leukemic bone marrow cells from each of two patients with B-cell lymphoid leukemias showed apparent translocations which appeared to be the result of telomeric association. In one patient, whole chromosomes were associated telomere to telomere in pairs; in the other patient, telomeres of whole chromosomes were associated with breakpoints located close to the proximal or distal ends of the heterochromatic band 1q12. Repeated base sequences, particularly (CA)n sequences, are believed to be the basis of telomere pairing, and likewise repeated base sequences of heterochromatin may explain the association of 1qh and telomeres. Telomeric association may be considered as a potential origin of new stable cytogenetic combinations that have a role in oncogene transposition and tumor etiology.
Adolescent↗
Karyotypic evolution in patients with acute myeloid leukemia.
Karyotypic evolution was found in 13 of 42 (31%) patients who were examined serially; if only those patients who were examined during successive stages of active leukemia were included, karyotypic evolution was revealed in 13 of 21 (62%). A further 6 patients showed multiple cytogenetic clones when leukemia was diagnosed. We did not find nonrandom chromosome involvement in the karyotypic changes, reported by others, notably trisomy #8. Our data for all patients who showed cytogenetic clones at some stage of their disease suggested that clones occurred with a higher incidence and arose earlier in patients with myeloblastic leukemia than in patients with myelomonocytic and monocytic leukemia. Patients showing karyotypic evolution tended to have longer than average survivals and to have had an abnormal karyotype when leukemia was diagnosed. The mode of preparation of hematologic samples, whether direct or cultured, has a bearing on karyotypic findings and could influence studies of karyotypic evolution.
Chromosome Aberrations↗
Reduced fertility in women with X chromosome abnormality.
One patient with the karyotype 46,X,del(X)(p11.23) and three patients with 45,X/46,XX mosaicism were fertile or showed normal ovarian function. The patient with the Xp deletion has two daughters with the same chromosomal abnormality. A study of these patients and of others reported in the literature indicated that fertility of patients with X chromosomal abnormality has a markedly shorter duration than fertility of the normal female. Menopause commonly occurred during the second and third decade of age. We suggest that such fertility is related to the rate of germ cell attrition and hypothesize that germ cell attrition in the human female is influenced by genes of multiple effect which are carried on the X chromosome. The more of these genes which are present the slower the rate of germ cell attrition.
Adolescent↗
Sex chromosome loss and clones characterized by autosomal abnormality in cultured corneal fibroblasts of man.
Cultured fibroblasts from 7 of 14 corneas showed loss of a sex chromosome in 20-100% of metaphase cells. An X chromosome was lost from female cells, a Y from male cells. Sex chromosome loss was more common in ophthalmologically abnormal corneas but did not show a strong correlation with donor age or with longer time in culture. Clones characterized by autosomal aneuploidy and aberrations were present in corneal cultures from seven donors. Their presence was not related to the incidence of sex chromosomal loss or prolonged culture time. Our results suggest that human corneal cells have a tendency toward loss of a sex chromosome and toward autosomal change, and that such cells form clones. It has yet to be determined if corneal cells undergo these cytogenetic changes and clone formation in vivo.
Adolescent↗
Nucleolar silver-staining patterns related to cell cycle phase and cell generation of PHA-stimulated human lymphocytes.
Silver staining (Ag-I) was used to investigate changes in the nucleolar structure of PHA-stimulated human lymphocytes through the phases of the cell cycle, G1, S and G2. Ag-I patterns and cell cycle phases of individual cells were assessed by sequential silver staining, Feulgen staining, DNA microdensitometry and 3H-thymidine autoradiography. The morphology and number of Ag-I nucleoli in a particular cell depended upon the phase of the cell cycle reached and on the number of generations the cell had passed through in culture. Resting, unstimulated cells usually had one small silver positive nucleolus. During blast transformation, the silver stained nucleoli increased in number and size, and then fused to form one very large, rounded or irregular-shaped nucleolus which was present through all cell cycle phases of the first reproductive cycle. Many lymphocytes developed a band-shaped nucleolus during their first S phase in culture. Lymphocytes at all cell cycle stages of the second and third generations after PHA-stimulation had multiple nucleoli whose combined areas approximated that of the single large nucleolus observed in first generation cells.
Cell Cycle↗
Duplication 8q syndrome due to familial chromosome ins(10;8)(q21;q212q22).
We describe a kindred in which an ins(10;8)(q21;q212q22) chromosome rearrangement has been segregating for at least four generations. The risk for balanced carriers to have offspring with duplication of 8q212 leads to 8q22 is about 0.31. Individuals with unbalanced chromosomes are mildly to moderately mentally retarded and have a similar unusual appearance. Other manifestations include highly arched or cleft palate (8/9), micrognathia (6/9), sloped shoulders (4-6/9), convulsions (4/9), camptodactyly (3/9), pectus excavatum (2/9), elbow contractures (1/9), and postaxial polydactyly (1/9). The appearance and habitus resemble the mosaic trisomy 8 syndrome, although other anomalies of mosaic trisomy 8, such as vertebral, patellar, and renal defects, were not demonstrated.
Abnormalities, Multiple↗
Retinoblastoma mutation rate in New Zealand and support for the two-hit model.
Age-specific incidence rates for 96 New Zealand patients with sporadic retinoblastoma peaked earlier for bilateral patients than for unilateral patients. The cumulative log survival until diagnosis for bilateral and unilateral patients followed linear and quadratic curves respectively, and supported the two-hit hypothesis for retinoblastoma. The germ cell mutation rate for retinoblastoma, assuming a single major gene, was calculated to be in the order of 9.3 X 10(-6) to 10.9 X 10(-6) for the New Zealand population.
Age Factors↗
Nonrandom cytogenetic changes in New Zealand patients with acute myeloid leukemia.
Bone marrow clones with abnormal chromosomes were observed in 56% of 66 patients with forms of acute myeloid leukemia [French-American-British (FAB) M1-M6]. Acute myeloblastic leukemia (AML, M1 and M2) was the most common form, and 65% of these patients showed chromosomal abnormalities compared with 41% of patients with acute myelomonocytic leukemia (AMMoL, M4). The recognized nonrandom chromosomal abnormalities found were trisomy 8, monosomy 5 or 7, trisomy 1q, t(6;9), t(8;21), t(15;17), and abnormalities in 17q. There was also a strong involvement of chromosome No. 11: Abnormalities were found in eight patients when their leukemia was diagnosed and in a further three patients during the course of karyotypic evolution. Six of these patients had AMMoL or AMoL. Complex or multiple clones were found in 37% of AML patients at diagnosis. Our AML patients had a reduced frequency of abnormalities in chromosome No. 5 or 7 and an increased frequency of abnormalities in chromosome No. 8 compared with studies reported in other countries (p = 0.01). This difference suggests that in New Zealand AML might be caused by factors different from those operating in more industrialized centers.
Bone Marrow↗
Direct versus cultured preparation of bone marrow cells from 22 patients with acute myeloid leukemia.
The 24-h culture of bone marrow from patients with acute myeloblastic leukemia (AML) and acute promyelocytic leukemia (APL) gave more analyzable metaphase cells and improved chromosome morphology compared with direct preparations. Culture increased the proportion of cytogenetically abnormal cells, and in six bone marrows were the direct preparation failed, a result was obtained from the cultured preparation. The culture of bone marrow from patients with APL led to the detection of clones carrying the t(15;17) that were not found in direct preparations. Such sequestered clones were not found in AML and acute myelomonocytic leukemia (AMMoL). Cultured preparations were no better than direct preparations from AMMoL.
Bone Marrow↗