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Biomedical subjects

B R Reeves

Publications and source records attributed to B R Reeves.

At least 19 recordsLinked to original sources
PubMed1998

Cryptic deletions and inversions of chromosome 21 in a phenotypically normal infant with transient abnormal myelopoiesis: a molecular cytogenetic study.

A case of transient abnormal myelopoiesis in a normal newborn without features of Down syndrome is described. The majority of bone marrow cells analysed belonged to a chromosomally abnormal clone with trisomy for chromosomes 18 and 21. Complex intrachromosomal rearrangements of one chromosome 21, demonstrated by fluorescence in situ hybridization using locus-specific probes, were found in a minor population of the clonal cells. These rearrangements involved loci previously shown to be rearranged in the leukaemic cells from patients with Down syndrome and leukaemia. However, the child's myeloproliferation resolved rapidly, with disappearance of the abnormal clone, and 3.5 years later she remains well.

Chromosome Aberrations↗
PubMed1997

Deletions of chromosome 21 restricted to the leukemic cells of children with Down syndrome and leukemia.

Down syndrome (DS) is associated with an increased risk of developing hematological malignancies, but the basis for this predisposition is so far unknown. Using fluorescence in situ hybridization with a panel of locus-specific probes on normal and leukemic metaphases, we have found long-arm interstitial deletions of one of the chromosome 21s in the leukemic cells from five patients with DS and leukemia. This finding provides strong evidence for a gene or genes present on chromosome 21 having an important function in the development of leukemia in individuals with Down syndrome.

Child, Preschool↗
PubMed1996

Haematological abnormalities in Shwachman-Diamond syndrome.

We have analysed the haematological parameters in 21 patients with Shwachman-Diamond syndrome (SDS) seen over a 25-year period at our institution. Neutropenia, although present in all patients, was intermittent in two-thirds, constant in the rest and was associated with impaired chemotaxis in all of those patients tested. Fetal haemoglobin (HbF) was elevated in 80% of the patients at some stage, and anaemia and thrombocytopenia was documented in 66% and 24% respectively. Bone marrow samples were taken in over half of the patients. Myelodysplastic syndrome (MDS) developed in seven (33%) patients, five of whom had acquired clonal structural chromosome abnormalities in their bone marrows. In five of the patients with MDS (24%) transformation to acute myeloid leukaemia occurred. Like other constitutional bone marrow failure syndromes. SDS has a predilection to leukaemic transformation hitherto assumed to be in the region of 5-10%. The data presented here suggest that this figure probably represents an underestimate. Shwachman-Diamond syndrome is an interesting model of leukaemia development and greater understanding of the clinical spectrum of this rare disorder should produce further insights into its pathobiology.

Adolescent↗
PubMed1995

Pediatric myelodysplasia: a study of 68 children and a new prognostic scoring system.

Clinical, morphologic, and cytogenetic features were examined in a group of 68 children with myelodysplasia (MDS) referred to a single institution between 1971-1991. The morphologic French-American-British (FAB) system of classification proved of limited value in this group of patients because 50% of the cases were categorized as chronic myelomonocytic leukemia and three patients with eosinophilia and MDS were unclassifiable. Cytogenetic analysis was performed in 63 cases and clonal abnormalities were detected in 55%; the most common chromosome involved was number 7. Modification of the FAB system to incorporate additional diagnostic features such as pretreatment fetal hemoglobin (Hb F) and cytogenetics allowed incorporation of the categories of juvenile chronic myeloid leukemia (JCML) and infantile monosomy 7 syndrome (IMo7). The resulting groups of patients had highly significant differences in survival (P = .00009). The overall 5-year survival for the patients was 31.9% (95% CI 21.7 to 44.1) and factors influencing prognosis included: modified FAB type, platelet count, Hb F level, and cytogenetic complexity. We developed a scoring system ("FPC") where each of the following findings at diagnosis scored one point: HbF greater than 10%, platelets < or = 40 x 10(9)/L, and complex karyotypic changes (two or more clonal structural/numerical abnormalities), which produced groups with highly significant differences, patients with a score of 0 having a 5-year survival of 61.6% (CI 33% to 84%), whereas those with a score of two or three all died within 4 years of diagnosis. The revised classification and scoring system may prove helpful in making treatment choices in pediatric MDS and now needs to be tested prospectively in large scale population-based studies.

Abnormalities, Multiple↗
PubMed1995

Kostmann's disease, recombinant HuG-CSF, monosomy 7 and MDS/AML.

Monosomy 7 (Mo7) and leukaemia predisposition are associated with Kostmann's disease (KD). The recent introduction of long-term recombinant HuG-CSF treatment in patients with KD, whilst showing significant reductions in infectious complications and improved quality of life, might also be associated with an increased risk of developing karyotypic abnormalities, myelodysplasia (MDS) and acute myeloid leukaemia (AML). We describe a case of an identical twin with probable autosomal dominant KD who developed anaemia, Mo7/MDS and AML at 18, 30 and 50 months respectively from starting r-metHuG-CSF (filgrastim) treatment. Further patient analyses are required to establish the natural history of KD and to determine what role, if any, filgrastim plays in altering the pathobiology of this disorder.

Agranulocytosis↗
PubMed1995

Two categories of synovial sarcoma defined by divergent chromosome translocation breakpoints in Xp11.2, with implications for the histologic sub-classification of synovial sarcoma.

Molecular analysis of a new series of synovial sarcomas confirms that t(X;18)(p11.2;q11.2) breakpoints occur at two distinct regions on Xp designated SS1 and SS2. Breakpoint position correlates with tumor phenotype. Monophasic tumors with no evidence of glandular components have breakpoints within the SS2 region in Xp11.21, and biphasic tumors with a focal poorly differentiated or extensive glandular structure have breakpoints within the SS1 region in Xp11.23.

Adolescent↗
PubMed1995

A case of acute megakaryoblastic leukaemia with t(X;6)(p11.21;q23) having an X chromosome breakpoint within a 450-Kb region which is also disrupted in two classes of solid tumours.

Karyotype analysis of a case of acute megakaryoblastic leukaemia revealed an X;6 translocation as the sole abnormality. Using fluorescence in situ hybridisation on leukaemic metaphases we demonstrated that the breakpoint on the X-chromosome occurred at p11.21, within a region spanned by a YAC probe which has also been found to be disrupted in synovial sarcomas and some papillary renal cell carcinomas.

Chromosome Mapping↗
PubMed1994

A case of acute monocytic leukemia with t(11;17) involving a rearrangement of MLL-1 and a region proximal to the RARA gene.

A case of acute monocytic leukemia with t(11;17)(123;q11-21) arising in a 4-month-old boy is described. The breakpoint on chromosome 11 could be mapped to an 8-kb BamHI fragment within the MLL-1 gene, as seen in the majority of infant leukemias. In situ hybridization with cosmid probes allowed us to map the breakpoint on 17q proximal to the RARA gene, while Southern and Northern analyses showed that the gene was not disrupted by the translocation.

Chromosomes, Human, Pair 11↗
PubMed1994

A case of myelodysplasia with eosinophilia having a translocation t(5;12) (q31;q13) restricted to myeloid cells but not involving eosinophils.

A chromosomally abnormal clone characterized by a translocation, t(5;12)(q31;q13), was detected in the marrow of a child with myelodysplasia and associated eosinophilia which included a generalized skin infiltration. Combined immunophenotyping and fluorescence in situ hybridization on interphase bone marrow cells showed that the chromosomal rearrangement was restricted to the granulocyte lineage but was not present in the eosinophils. If the chromosome rearrangement is important in the overproduction of eosinophils in this case, the lineage restriction found suggests that its effect must be indirect.

Bone Marrow↗
PubMed1993

Leukaemia arising in donor cells following allogeneic bone marrow transplantation for beta thalassaemia demonstrated by immunological, DNA and molecular cytogenetic analysis.

Combined DNA analysis, molecular cytogenetic and immunological techniques have been used to identify the donor origin of common acute lymphoblastic leukaemia (cALL) which arose in a male patient with beta thalassaemia major, 5 years after an allogeneic bone marrow transplant from his HLA-matched sister. The necessity of using multiple techniques in this and similar cases is emphasized and the possible mechanisms for the development of donor leukaemia and the leukaemic transformation of donor cells are discussed.

Bone Marrow↗
PubMed1992

Localization of the synovial sarcoma t(X;18)(p11.2;q11.2) breakpoint by fluorescence in situ hybridization.

A high proportion of synovial sarcomas contain a chromosome translocation t(X;18)(p11.2;q11.2). We have previously used somatic cell hybrids derived from an established cell line, SS255, to map the X chromosome breakpoint to the interval flanked by the markers DXS14 and DXS146. In this study we have examined these hybrids with thirteen additional markers located at Xp11.3-Xcen, by Southern hybridization. Based on these results we have delimited the breakpoint as follows Xpter-DXS228-(UBE1-OATL1-TIMP-DXS226 )-(DXS255-TFE3-ELK1-DXS146)-OATL2- X;18-(DXS14-DXS422-DXS423-DXS674-DXS679)-+ ++Xcen. Confirmation of the breakpoint location has been obtained by analysis of two synovial sarcoma cell lines, SS255 and HA2243, using fluorescence in situ hybridization. A 350kb YAC probe spanning the DXS423 locus hybridized only to the derivative X chromosome, showing that it maps proximal to the breakpoint. Two YAC probes of 300kb and 450kb, containing the OATL2 locus, hybridized to both derivative chromosomes, indicating that these YACs span the translocation breakpoint. Similar results were obtained with both cell lines. The identification of YACs that span the t(X;18) breakpoint now facilitates a strategy for cloning candidate genes from this precisely defined region.

Animals↗
PubMed1991

A case of cerebellar medulloblastoma with a single chromosome abnormality.

In the few published karyotypes of human medulloblastoma, multiple chromosome abnormalities have usually been demonstrated. We report a case of medulloblastoma in which only a single structural alteration was observed, namely an unbalanced translocation between chromosomes 1 and 6 resulting in partial 1q trisomy and partial 6q mónosomy. This finding may help define genomic regions that are of importance in development of medulloblastoma.

Cerebellar Neoplasms↗
PubMed1990

Serial cytogenetic studies showing persistence of original clone in Hodgkin's disease.

A case of Hodgkin's disease is described in which cytogenetic studies were performed at intervals for 5 years. Clonally related chromosomally rearranged cells persisted during that time, with emergence of more complex karyotypes in the terminal phase of the disease. The chromosome findings are discussed in relation to the limited data available on banded karyotypes in Hodgkin's disease.

Bone Marrow Cells↗
PubMed1989

Cytogenetic abnormalities in human ependymomas.

The karyotypes of 4 human ependymomas have been determined. In one ependymoma, translocations involving chromosomes 9, 17 and 22 were observed together with the loss of the normal chromosome 17. A second ependymoma had many chromosomal alterations that included a translocation between chromosomes 1 and 2 and re-arrangements involving chromosome 17. No major consistent alterations were detected in the remaining 2 cases. Our karyotypes do not resemble the few previously published karyotypes of ependymomas, but had features, such as the alterations involving chromosome 17, that were similar to those of other brain tumours in children.

Brain Neoplasms↗
PubMed1989

Cytogenetic studies of 21 patients with acute lymphoblastic leukemia in relapse.

Karyotypes of 21 patients, originally entered into the Third International Workshop on Chromosomes in Leukemia (3IWCL), were investigated in first, second and/or subsequent relapses. Karyotypes at diagnosis were related to the relapses in the following ways: normal to normal (N-N) (five cases); abnormal to normal (A-N) (two cases); abnormal to abnormal with no change (A-A) (five cases); abnormal to abnormal with clonal evolution (A-A+) (eight cases); and normal to abnormal (N-A) (one case). The A-A group comprised two each of t(4;11) and t(9;22) cases and one pseudodiploid case; included in this group were the only two patients who did not receive intensive treatment. Both A-N cases had been pseudodiploid at diagnosis. Clonal evolution A-A+ occurred in patients who had had 47-49 chromosomes or pseudodiploidy at diagnosis and was mainly due to the addition of structural change. The additional abnormalities were different in each case. The only de novo appearance of a clone (N-A) was in host cells in relapse following bone marrow transplantation. Clonal evolution occurred in patients who had been intensively treated and who relapsed late; the median time from diagnosis to relapse studied for the A-A group was 6 months and for the A-A+ group was 24 months. Survival following relapse was shorter for patients who had had a clonal abnormality at any time (median 10 months) than for those with no abnormality at diagnosis or in relapse (median 26 months).

Adolescent↗
PubMed1989

Cytogenetic studies of 103 patients with acute myelogenous leukemia in relapse.

In order to investigate the cytogenetic patterns in relapsed acute myelogenous leukemia (AML), a clinical and cytogenetic follow-up of patients newly diagnosed for the Fourth International Workshop on Chromosomes in Leukemia (4IWCL) was evaluated at the 6IWCL. Information was received on 103 patients in relapse who were then classified into seven groups according to the diagnostic karyotype. These groups were: normal, t(8;21), t(15;17), +8, a single specific abnormality either numerical or structural other than those already listed, a single nonrandom or miscellaneous abnormality again either numerical or structural, and complex abnormalities. The patient's age, diagnostic FAB type, the number of relapses, the total survival time, and the karyotype in relapse were considered in each of these cytogenetic groups. The remission and survival rates were comparable in all groups except the +8 group, where patients relapsed earlier and had a shorter survival time. Multiple relapses occurred most frequently in the t(8;21) group, whereas none of the patients with t(15;17) relapsed more than once, although the total survival time was similar to the two groups. Thirty-nine percent of the patients relapsed with the same karyotype as at diagnosis. A more complex karyotype showing evolution was found in 53%, and 8% showed either a less-complicated karyotype or appeared to have reverted to normal. Numerical abnormalities in relapse frequently involved trisomy of chromosomes 8 and/or 21. There was a nonrandom development of 9q- with relapse in patients with t(8;21). A pericentric inversion of chromosome 4, and abnormality infrequently reported at diagnosis, was found in relapse in association with t(15;17), t(8;21), and +8 karyotypes. Changes considered to be typically secondary in nature involving 5q, 7q, and 12p were seen in only seven cases. Twenty-one patients who had an apparently normal karyotype at diagnosis remained normal in relapse, indicating that absence of clonal chromosome abnormality is a real observation in AML rather than a failure of detection.

Adolescent↗
PubMed1989

The clinical significance of karyotype in acute myelogenous leukemia.

To evaluate further the prognostic significance of karyotype at diagnosis of acute myelogenous leukemia (AML), we have made a follow-up study of 711 patients who were diagnosed between January 1, 1980, and March 31, 1982, and who were originally reported by the Fourth International Workshop on Chromosomes in Leukemia (4IWCL). Three different chromosomal classifications were evaluated, including presence of normal and abnormal metaphases (NN-AN-AA classification), a modification of the Chicago classification, and a complexity classification. All three chromosomal classifications were shown to correlate significantly with outcome in patients with de novo AML. Furthermore, the NN-AN-AA classification and the complexity classification had independent prognostic significance when age, sex, and FAB morphology were also considered in multivariate analyses of survival. These data provide further evidence that karyotype is an important factor in predicting the outcome of patients with AML.

Adolescent↗