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P H Fitzgerald

Publications and source records attributed to P H Fitzgerald.

At least 37 records · Page 2Linked to original sources
PubMed1989

Localization of human c-mos to chromosome band 8q11 in leukemic cells with the t(8;21) (q22;q22).

Chromosome in situ hybridization studies locate c-mos to chromosome band 8q11 in leukemic cells carrying the t(8;21) (q22;q22). This amends the previous assignment of c-mos to chromosome band 8q22 and conforms with its recent assignment to 8q11 in normal cells and in a cell line with a structurally abnormal chromosome 8. C-mos lies proximally to, and distant from, the breakpoint at 8q22 in the t(8;21) and is unlikely to have a role in the onset of acute myeloid leukemia characterized by this translocation.

Adult↗
PubMed1989

The oncogene ETS1 is distant from the chromosome 11 breakpoint in leukaemic cells with the t(11;19)(q23;p13).

Field inversion gel electrophoresis of DNA from a leukemic clone characterized by the t(11;19)(q23;p13) allowed us to exclude any genomic rearrangement within more than 900 kb of DNA encompassing ETS1 on chromosome 11. Although ETS1 was moved to the derivative chromosome 19 as a result of the t(11;19), we conclude that this oncogene is not close to the chromosome 11 breakpoint and is unlikely to be involved in this leukaemia.

Blotting, Southern↗
PubMed1989

HRAS1 and INS genes are relocated but not structurally altered as a result of the t(7;11)(p15;p15) in a clone from a patient with acute myeloid leukaemia (M4).

A patient whose leukaemic cells carried the rare t(7;11)(p15;p15) was diagnosed as having acute myelomonocytic leukaemia (AML-M4), and supports the association of this specific translocation with forms of acute myeloid leukaemia showing differentiation. Blast phase chronic myeloid leukaemia was excluded by lack of involvement of the ABL and BCR genes. Chromosome in situ hybridization studies showed that both the HRAS1 and INS genes were present on the terminal part of chromosome 11p which was translocated to chromosome 7p. Neither HRAS1 nor INS were structurally rearranged. Field inversion gel electrophoresis showed that a 400 kb fragment encompassing HRAS1 was structurally entire in leukaemic DNA. Because the INS gene, which was also translocated, is probably located proximal to HRAS1 on chromosome 11p, it is unlikely that HRAS1 was near the chromosome 11 breakpoint or involved in this leukaemia.

Cells, Cultured↗
PubMed1989

Involvement of immunoglobulin heavy- and light-chain (kappa) gene clusters in a human B-cell translocation, t(2;14).

The breakpoints of a translocation, t(2;14)(p11;q32), detected in an Epstein-Barr virus-transformed lymphoid B-cell line were mapped by Southern analysis, field-inversion gel electrophoresis, and in situ hybridisation. The translocation involved the immunoglobulin light-chain (kappa) locus on chromosome 2 and the heavy-chain locus on chromosome 14. The breakpoint on chromosome 2 was between VK and CK, most likely within JK. The chromosome 14 break was located within the VH cluster, no more than 220 kb 5' of the productively rearranged JH locus. The translocation probably resulted from an aberrant rearrangement of the kappa light-chain genes.

B-Lymphocytes↗
PubMed1989

Localization of the SRC oncogene to chromosome band 20q11.2 and loss of this gene with deletion (20q) in two leukemic patients.

In situ hybridization of the pHul-c-src probe to metaphase cells from three normal donors and two leukemic patients showed significant labeling in the proximal region of the long arm of chromosome 20q, with modal peaks of grains consistently at band 20q11.2. A secondary peak of grains was detected in the region 20q13.2-qter, the localization of SRC suggested by previous in situ studies. The exact localization of SRC is important for understanding the del(20q) chromosomal abnormality in myeloid neoplasias. Chromosome in situ hybridization and genomic studies showed loss of one allele of SRC in two patients with the deletion (20q). These results differ from previously published findings and suggest heterogeneity of the breakpoint at 20q11.2 in interstitial deletions of 20q, which characterize myeloid disorders.

Adult↗
PubMed1988

A cytogenetic and molecular analysis of five variant Philadelphia translocations in chronic myeloid leukemia.

Three patients had complex translocations involving 9q34, 22q11, and a third chromosome (Xq11, 7q11.2, or 15q11.2). Two patients had apparently simple variant Philadelphia (Ph) translocations, t(19;22) and t(11;22), with no obvious involvement of chromosome 9, and the Ph was masked in the t(11;22). In situ hybridization studies showed transposition of the abl gene from chromosome 9q34 to the breakpoint cluster region (bcr) of chromosome 22 in all five patients; this was confirmed by rearrangements of the bcr gene in leukemic DNA. In situ hybridization also showed that the bcr-3' and c-sis probes consistently translocated to recipient chromosomes X, 1, 7, 11, and 15, whereas IgC lambda remained on chromosome 22q. These results confirm that association of abl and bcr is a consistent feature of chronic myeloid leukemia irrespective of the cytogenetic presentation and support the conclusion of Hagemeijer that all simple variant Ph translocations are, in fact, complex and involve at least three chromosomes.

Adult↗
PubMed1988

Abnormal chromosome 16 in clonogenic eosinophils from a case of acute myeloid leukemia (FAB,M2).

A case of acute myeloid leukemia (AML, FAB M2) is described in which the leukemic karyotype showed several numerical and structural cytogenetic abnormalities including an abnormal chromosome 16 with breakpoint at band q22, monosomy for chromosomes 5 and 7, and a single pair of double minute chromosomes. There was no patient history of treatment for a previous malignancy or occupational exposure to mutagens. Bone marrow eosinophilia was seen at presentation for refractory anemia with excess blasts in transformation and when AML was diagnosed. When bone marrow buffy coat cells were cultured in soft agar in the presence of colony stimulating factor, 19% of the colonies and 20% of the clusters were of eosinophils. Cytogenetic examination of pooled eosinophil colonies showed the marker chromosomes that identified the leukemic population.

Bone Marrow↗
PubMed1988

An identical t(Y;1)(q12;q21) in two patients with myelodysplastic syndromes.

Two male patients with myelodysplastic syndromes, one with refractory anemia with excess blasts (RAEB), the other with chronic myelomonocytic leukemia both had in their bone marrow and peripheral blood cells the same abnormal karyotype 46,X,-Y, + der (Y)t(Y;1)(q12;q21). This abnormality produced trisomy for the 1q21-1qter region of chromosome 1. In addition to the t(Y;1), the patient with RAEB had a del(20)(q11) abnormality in separate CFU-GM and BFUe progenitor cell populations. The t(Y;1) clone of this patient underwent chromosomal evolution with the acquisition of trisomies for chromosomes 2, 6, 8, and 9. Cytogenetic analysis of serial peripheral blood samples showed that the t(Y;1) clone and its derivatives gradually replaced that with the 20q- abnormality. Metaphase cells trisomic for chromosomes 2, 6, 8, and 9 were found predominantly in the CFU-GM population and only rarely in BFUe colonies, suggesting that chromosomal evolution was largely confined to the granulocytic lineage.

Aged↗
PubMed1988

Essential thrombocythaemia and the Philadelphia chromosome.

Six adult patients presented with clinical features of essential thrombocythaemia. Five of the patients, although Ph-positive, have maintained these features without evidence of leukaemia; in one case for 9 years. A sixth patient developed leukaemic blast crisis following a persistently high platelet count over 4 years. Her cells were Ph-negative, but hybridization of gene probes to chromosomes in situ and to leukaemic DNA showed that the abl oncogene had moved to the breakpoint cluster region (bcr) on the normal chromosome 22. This patient has the same molecular gene change as occurs in some cases of Ph-negative chronic myeloid leukaemia (CML) whose leukaemic cells likewise show no evidence of chromosomal translocation. Molecular studies are essential for the correct diagnosis of these patients. The Ph genomic lesion appears to have a range of leukaemic expression which includes thrombocythaemia as well as chronic myeloid leukaemia and acute lymphatic leukaemia.

Adult↗
PubMed1988

Acquired homozygosity of the rearranged bcr allele during the acute leukemic phase of a patient with Ph-negative chronic myeloid leukemia.

A 45-year-old male patient with Ph-negative chronic myeloid leukemia (CML) had rearranged bcr-3' and bcr-5' gene regions in Southern blot studies when leukemia was diagnosed. During development of terminal blast crisis, successive blood samples showed a progressive decrease in the amount of germline bcr DNA and its complete loss by full blast crisis. There were also increased amounts of rearranged bcr DNA consistent with acquired homozygosity. A similar result was obtained with an IgV lambda probe and indicated homozygosity of a significant part of chromosome 22. The bcr-abl gene complex behaves as a somatic dominant in CML, and we suggest that its acquired homozygosity is a mechanism of bcr-abl amplification similar to duplication of the Ph chromosome commonly found in the blast crisis of CML.

Alleles↗
PubMed1988

Basophils exhibit rearrangement of the bcr gene in Philadelphia chromosome-positive chronic myeloid leukemia.

Basophils were isolated from the peripheral blood of two patients with Philadelphia positive-chronic myeloid leukemia using monoclonal antibody Bsp-1 and fluorescence activated cell sorting. DNA blot analyses demonstrated rearrangement of the breakpoint cluster region gene in the isolated basophils, which suggests their leukemic origin. Isolated T cells from these patients that were cultured for 14 days in the presence of interleukin-2 lacked rearrangement of the breakpoint cluster region gene and are therefore unlikely to be derived from the chronic myeloid leukemia clone.

Basophils↗
PubMed1988

Transposition of the oncogene c-ets-1 in a t(11;19)(q23;p13) cell line transient during clonal evolution of blast crisis chronic myeloid leukemia.

A patient with Ph-negative chronic myeloid leukemia showed active karyotypic evolution when he entered blast crisis. One cell line, which predominated briefly in an accelerated myeloid phase, was characterized by the t(11;19)(q23;p13). Chromosome in situ hybridization demonstrated movement of the oncogene c-ets-1 from the der (11q-) to the der (19p+). The breakpoint at 19p13 was in the vicinity of the human insulin receptor gene locus (INSR). No rearrangements of the c-ets and INSR genes were found in Southern blot analyses. Myeloid lineage was indicated by cell morphology and absence of immunoglobulin JH gene rearrangement and was supported by loss of the germ line bcr-3' gene. Chromosome rearrangements involving 11q23 and movement of c-ets-1 characterize monocytic and lymphoid leukemias and have not previously been reported in myeloid blast crisis of chronic myeloid leukemia.

Cell Transformation, Neoplastic↗
PubMed1987

Sustained complete remission in Richter's syndrome.

Richter's syndrome is the development of an aggressive diffuse lymphoma in chronic lymphatic leukemia (CLL) and is associated with a poor prognosis. A patient with CLL developed Richter's syndrome, which responded to intensive chemotherapy. Spontaneous regression of CLL in blood and marrow was observed at the onset of Richter's syndrome. The patient remained in complete remission from the lymphoma 4 years after the completion of treatment, and there was no evidence of CLL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Complexity of an apparently simple variant Ph translocation in chronic myeloid leukemia.

A patient with chronic myeloid leukemia (CML) presented with an apparently simple Ph translocation t(19;22)(q13;q11). In-situ hybridization revealed movement of the c-abl oncogene from a cytogenetically normal chromosome 9 to the Ph. Bcr-3' and c-sis probes hybridized to distal 1p and not to the 19q+ chromosome as expected from the cytogenetic findings. We concluded that this patient had a complex translocation involving four chromosomes: t(1;9;19;22)(p36;q34;q13;q11).

Adult↗
PubMed1987

A characteristic CFU-GM growth pattern in acute promyelocytic leukemia.

Bone marrow and/or peripheral blood cells from 12 patients with acute promyelocytic leukemia (APL) were cultured in soft agar or methylcellulose in the presence of 15% human placental conditioned medium as a source of colony stimulating factor. Buffy coat cells, taken from ten patients when APL was diagnosed, produced a growth pattern in soft agar that was characterized by a high incidence of small, relatively uniform clusters of promyelocytes, which, when stained in situ, reacted strongly with myeloperoxidase, Sudan black B and chloroacetate esterase. In six cases, the leukemic origin of the cluster forming cells was demonstrated by the presence of the t(15;17) in these cells. During periods of complete remission the small clusters were replaced by larger and more diverse aggregates which had a normal karyotype. At relapse the small cluster growth pattern returned. The growth pattern of small clusters is more commonly associated with APL than with other types of acute myeloid leukemia.

Adult↗
PubMed1987

Karyotypic evolution in a B-cell lymphoma.

A B-cell lymphoma in the lung of a 59-year-old woman showed a near-pentaploid karyotype and chromosomal changes indicating a t(8;14) in cells from a pleural aspirate. Cells from metastases to the skin and a second pleural aspirate were pseudodiploid, but showed separate further complex cytogenetic changes. Among these was a 14q+ chromosome, but the #8 chromosomes apparently were normal. It is suggested that there was a loss of the derivative 8q- chromosome from the t(8;14) followed by homozygozity of the normal #8 chromosome.

Aged↗