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Biomedical subjects

K F Wong

Publications and source records attributed to K F Wong.

At least 73 records · Page 4Linked to original sources

Translocation (12;17)(q13;q23) in de novo acute myeloid leukemia with trilineage myelodysplasia.

12q13 abnormalities have been reported to be associated with a variety of benign and malignant solid tumors. Recently, they have been shown to be a nonrandom karyotypic change in acute myeloid leukemia. We report a case of de novo acute myeloid leukemia with trilineage myelodysplasia showing t(12;17)(q13;q23) as the sole chromosomal abnormality. A review of the literature indicates that 12q13 translocation in acute myeloid leukemia is often associated with concomitant dysmyelopoietic changes. There is also evidence to suggest that 12q13 translocation occurs more frequently in acute myeloid leukemia with a prior history of mutagenic exposure or karyotypic indicators of secondary leukemia.

Acute Disease↗

Mantle cell lymphoma in leukemic phase: characterization of its broad cytologic spectrum with emphasis on the importance of distinction from other chronic lymphoproliferative disorders.

BACKGROUND: Mantle cell lymphoma is a mature, virgin B-cell neoplasm characterized immunologically by a panB+, CD5+, CD23-, cyclin D1+ phenotype and genetically by t(11;14)(q13;q32) with overexpression of the cyclin D1 (bcl-1) gene. It usually presents as advanced stage disease, involving lymph nodes, spleen, bone marrow, and extranodal sites, particularly the gastrointestinal tract. However, frank leukemic presentation with high white cell counts is uncommon and can be difficult to distinguish from other chronic lymphoproliferative disorders. The aim of this study was to characterize the morphologic spectrum of leukemic mantle cell lymphoma. METHODS: During the period July 1994 through October 1998, 14 patients with mantle cell lymphoma in leukemic phase were diagnosed at the Department of Pathology, Queen Elizabeth Hospital, Hong Kong. The diagnosis of mantle cell lymphoma was based on histologic and immunocytochemical findings and was confirmed by cyclin D1 immunoreactivity in all cases. The clinical records and laboratory results were reviewed. Peripheral blood smears, bone marrow, and other tissue biopsies were examined, with particular attention to the cytologic features of the leukemic mantle cells. RESULTS: Mantle cell lymphoma in leukemic phase showed a very aggressive clinical course. Eight patients died at a mean of 13 months, and only 1 patient was disease free. Morphologically, the leukemic mantle cells exhibited a broad morphologic spectrum, with several cytologic patterns identified: 1) mixed small and medium-sized cells, 2) predominantly medium-sized cells, 3) predominantly large cells, and 4) giant cells. Despite variations in the size and nuclear shape, the leukemic mantle cells could usually be recognized by the nuclear irregularity and clefting, moderately dense but evenly distributed chromatin, small nucleoli, and scant cytoplasm. CONCLUSIONS: Recognition of the characteristic cytologic features of leukemic mantle cells can help to distinguish them from other chronic lymphoproliferative disorders. In contrast to the latter, the clinical course is aggressive and response to conventional chemotherapy is poor.

Aged↗

A man with natural killer cell lymphoma showing 46,XX and deletion 6q.

Specific chromosomal abnormalities have been shown to be associated with certain types of leukemia and lymphoma. We and others have recently demonstrated del(6)(q21q25) as being strongly associated with natural killer cell lymphoma/leukemia. In this report, we describe a case of natural killer cell lymphoma with a clonal chromosomal abnormality of 46,X,-Y,+X,t(2;9)(q31;p24), del(4)(q21q25),del(6)(q21q23), and propose that the region 6q23 is probably an important site of genetic alteration in this group of tumors.

Adult↗

Factors influencing uptake and retention of amino-containing drugs in large unilamellar vesicles exhibiting transmembrane pH gradients.

The level of uptake and retention of amino-containing drugs in large unilamellar vesicles (LUVs) following uptake in response to a transmembrane pH gradient (DeltapH) can vary dramatically depending on the drug. For example, the anticancer drugs doxorubicin and epirubicin can be readily retained, whereas the anticancer drug vincristine and the antibiotic ciprofloxacin tend to leak out rapidly. In this investigation, we examine the influence of the hydrophobicity of the entrapped amines (that induce the DeltapH) and the anionic lipid content of the LUV on drug retention. It is shown that entrapment of increasingly hydrophobic monoamines (methylamine to amylamine) all lead to an induced DeltapH of 3 units and essentially complete drug uptake under the conditions employed, but do not lead to improved retention of vincristine and ciprofloxacin. However, significantly improved retention could be achieved by substitution of the anionic lipid distearoylphosphatidylglycerol (DSPG) for distearoylphosphatidylcholine (DSPC) in the LUV bilayer. Further, it is shown that if the induced DeltapH is reduced to 1.4 units (driven by entrapped diamine) nearly 100% accumulation of doxorubicin and epirubicin could be achieved, whereas only 25% loading for vincristine and ciprofloxacin was observed. Taken together these results provide methodology for improving (weak base) drug retention in liposomes and indicate that drugs that can partition into the lipid bilayer exhibit improved uptake and retention characteristics.

Amines↗

Comparative genomic hybridization analysis of natural killer cell lymphoma/leukemia. Recognition of consistent patterns of genetic alterations.

Putative natural killer (NK) cell lymphoma/leukemia is a rare group of recently characterized hematolymphoid malignancies. They are highly aggressive and frequently present in extranodal sites, including the nasal area and the upper aerodigestive system, and nonnasal areas such as the skin and the gastrointestinal tract. According to clinicopathological features, they can be classified into nasal NK cell lymphoma, nasal-type NK cell lymphoma occurring in nonnasal areas, and NK cell lymphoma/leukemia. Genetic alterations in NK cell lymphoma/leukemia are not well defined. In this study, we have performed comparative genomic hybridization (CGH) on DNA extracted from fresh or frozen tissues of 10 patients with NK cell lymphoma/leukemia. They comprised four nasal NK cell lymphomas, one nasal-type NK cell lymphoma, and five NK cell lymphomas/leukemias. CGH showed frequent deletions at 6q16-q27 (four cases), 13q14-q34 (three cases), 11q22-q25 (two cases), 17p13 (two cases), and loss of the whole chromosome X (two cases). DNA amplification was observed in a majority of the chromosomes. Five cases showed DNA gains at region 1p32-pter. Frequent DNA gains were also found in chromosomes 6p, 11q, 12q, 17q, 19p, 20q, and Xp (three cases each). Interestingly, DNA gains were more frequent in nasal/nasal-type NK cell lymphomas than NK cell lymphoma/leukemia. These genetic alterations correlated well with karyotypic features found in some of the cases. The frequent DNA losses at 6q and 13q suggest that the presence of tumor suppressor genes at these regions is important in NK cell transformation. In addition to establishing novel patterns of genomic imbalances in these rare NK cell malignancies, which may be targets for future molecular analysis, this study also provides important information on genetic alterations in NK cell lymphomas that may be useful in defining their positions in current lymphoma classification schemes, which are increasingly focusing on phenotypic and genotypic correlations.

Adolescent↗

Trisomy 22 in acute myeloid leukemia: a marker for myeloid leukemia with monocytic features and cytogenetically cryptic inversion 16.

Trisomy 22 is an uncommon chromosomal abnormality in acute myeloid leukemia. Recent studies, however, have shown an association between trisomy 22 and acute myeloid leukemia with a monocytic component, and in particular, acute myelomonocytic leukemia with marrow eosinophilia. Furthermore, it has also been suggested that trisomy 22 was in fact only a secondary chromosomal change occurring in acute myeloid leukemia with inv(16). In this report, we analyze the morphological, cytogenetic, and molecular findings of three cases of acute myeloid leukemia with trisomy 22 but without cytogenetic evidence of inv(16). The results indicate a consistent association between trisomy 22 and inv(16), the latter being cytogenetically cryptic in some cases. This finding is of potential diagnostic and therapeutic significance.

Acute Disease↗

BCR/ABL translocation in adult acute lymphoblastic leukemia: a comparison of conventional and interphase cytogenetic studies.

Twenty-four adult Chinese patients with de novo acute lymphoblastic leukemia (ALL) were studied for the BCR/ABL translocation using both conventional cytogenetics and fluorescence in situ hybridization (FISH). Eight (33%) patients had the translocation as shown by FISH and all were B-lineage ALL (8/19, 42%). Conventional cytogenetics revealed a t(9;22)(q34;q11) in six of them, but was either unsuccessful, or not done in the other two. Seven of the eight positive cases (88%) showed a breakpoint at the minor breakpoint cluster region (m-BCR), which was confirmed by reverse transcriptase polymerase chain reaction (RT-PCR). To conclude, the frequency of BCR/ABL translocation in Chinese patients with de novo ALL is comparable to patients in the Western hemisphere, in contrast to a previous report. The predominance of m-BCR/ABL fusion among these Chinese patients with BCR/ABL translocation is also similar to patients in the Western population. Fluorescence in situ hybridization is a sensitive, specific and relatively simple technique for demonstrating this important unfavorable prognostic marker in ALL, even in a routine service laboratory setting.

Adult↗

Cytogenetic abnormalities in chronic B-cell lymphoproliferative disorders in Chinese patients.

We analyzed the cytogenetic findings of 59 Chinese patients with chronic B-cell lymphoproliferative disorders. More than half of the patients (n = 36, 61%) had chronic lymphocytic leukemia. Cytogenetic abnormalities were demonstrated in 44.1% (26/59) of the patients. Trisomy 12 was the most frequent abnormality in chronic lymphocytic leukemia and was found in 27.8% (10/36) of the patients, indicating that the incidence of trisomy 12 in chronic lymphocytic leukemia in Chinese patients might not be low compared with the West as previously suggested. Structural abnormalities involving chromosomes 13 at band q14 were the next most common abnormalities in patients with chronic lymphocytic leukemia. Among the 11 patients with mantle cell lymphoma in leukemic phase, t(11;14) was seen in only 2 patients (18.2%). Several unusual cytogenetic abnormalities also were found.

Adult↗

T-cell prolymphocytic leukemia with a novel translocation (6;11)(q21;q23).

T-cell prolymphocytic leukemia (T-PLL) is an uncommon chronic lymphoproliferative disorder characterized by lymphadenopathy, splenomegaly, and lymphocytosis. The leukemic cells have the appearance of prolymphocytes and usually an immunophenotype of T-helper cells (CD3+ CD4+ CD8-). Inv(14q), del(11q), i(8q), and rearranged Xq28 are the commonest nonrandom chromosomal abnormalities in T-PLL. Recently, it has been shown that the ataxia-telangiectasia mutated (ATM) gene located at 11q23 is often deleted in T-PLL, suggesting a tumor suppressor role of the ATM gene on tumorigenesis of T-PLL. We report a case of T-PLL with t(6;11)(q21;q23) as the sole chromosomal abnormality and suggest that the cytogenetically identified translocation also implicates the ATM gene.

Aged↗

11q13 is a cytogenetically promiscuous site in hematologic malignancies.

11q13 translocation has been described in mantle cell lymphoma in the form of t(11;14) (q13;q32), with rearrangement and over-expression of the cyclin D1 gene. Recently, an association between 11q13 and acute myeloid leukemia is recognized. We describe the occurrence of 11q13 translocations in both acute leukemias and myelodysplastic syndrome, and suggest that other genetic mechanisms unrelated to cyclin D1 may be involved in the tumorigensis. Furthermore, 11q13 appears to be a cytogenetically promiscuous site involved in reciprocal translocations with different chromosomes in both myeloid and lymphoid malignancies.

Acute Disease↗

Cytogenetic divergence of the same blastic clone in transformed chronic granulocytic leukemia: no effect on morphologic and immunologic features.

A 19-year-old man with Ph-positive chronic granulocytic leukemia developed lymphoblastic transformation. Cytogenetic evolution was observed, with an abnormal clone showing i(17q) together with the t(9;22). Chronic phase of the chronic granulocytic leukemia were re-established with systemic chemotherapy, which also led to disappearance of the clone with i(17q). However, the acute lymphoblastic leukemia relapsed after 6 weeks, with the emergence of a phenotypically and genetically identical but cytogenetically distinctive clone. Our findings suggest that cytogenetic evolution in transformed chronic granulocytic leukemia reflects only the instability of the blastic clones, and may not determine its phenotypic differentiation.

Adult↗

Chronic myelomonocytic leukemia with t(7;11)(p15;p15) and NUP98/HOXA9 fusion.

Translocation (7;11)(p15;p15) is a recently characterized chromosomal abnormality that results in fusion of the NUP98 gene on 11p15 and the HOXA9 gene on 7p15. It shows a strong racial predisposition, being found predominantly in Oriental patients, and has been reported almost exclusively in acute myeloid leukemia, often with associated myelodysplastic changes. In this report, we describe the unique occurrence of t(7;11)(p15;p15) and NUP98/HOXA9 fusion in a patient with chronic myelomonocytic leukemia, and suggest that the genetic lesion may involve multipotential myeloid stem cells.

Adult↗

The use of critical pathways in caring for schizophrenic patients in a mental hospital.

To provide quality health care and at the same time, to control cost, literature suggests that using critical pathways as a tool can enhance resource management, increase collaborative practice, and benefit patient care. This study describes the processes of developing a critical pathway in caring for schizophrenic patients in a mental hospital in Hong Kong. The perceived benefits and difficulties in using the critical pathway are discussed from a nursing perspective. Nurses believed that the use of critical pathways could improve the coordination and effectiveness of care. Also, nurses' autonomy and professional status improved. However, inadequate knowledge and resistance from other disciplines were barriers to the implementation. Recommendations are given to overcome the barriers.

Cost Control↗

Chromosome aberrations are restricted to the CD56+, CD3- tumour cell population in natural killer cell lymphomas: a combined immunophenotyping and FISH study.

Natural killer (NK) cell lymphomas are a newly recognized entity of non-Hodgkin's lymphoma with a highly aggressive clinical course and strong association with Epstein-Barr virus (EBV) infection. Although no recurrent chromosome aberrations have been identified in NK-cell lymphoma, deletions of 6q and trisomy 7 have been described repeatedly in this type of lymphoma. In this study we attempted to determine the immunophenotypes of tumour cells with certain chromosome aberrations, i.e. deletions of 6q and trisomy 7, in three cases of NK cell lymphomas by means of combined immunophenotyping and fluorescence in situ hybridization (FISH). In all three cases clonal chromosome aberrations were detected only in CD56+ cells but not in CD3+ or CD5+ cells. However, not all CD56+ cells were shown to contain these chromosome aberrations. Double immunophenotyping combined with FISH confirmed that the chromosome aberrations occurred only in CD56+CD3- cells. This study indicates that chromosome aberrations in NK-cell lymphomas are restricted to the CD56+, CD3- and CD5- cell population and that NK-cell lymphomas are indeed derived from mature true NK cells and not from T lymphocytes.

Adult↗

The differentiating effect of retinoic acid and vincristine on acute myeloid leukemia.

We have shown previously that granulocytic maturation and differentiation occurred when HL-60 cells and leukemia cells from a patient with acute promyelocytic leukemia (APL) were exposed to all-trans retinoic acid (ATRA) after treatment with a noncytotoxic concentration of vincristine (VCR), suggesting that VCR might have synergistic action with ATRA in the treatment of APL. Leukemic cells obtained from 24 patients with AML were exposed to 20 nM VCR for 1 h, followed by 1 microM ATRA for 6 days. Changes in the expression of myeloid leukocyte antigens were observed using flow cytometry. Differentiation phenotype as determined by the decrease or increase in maturation cell marker was observed in three samples treated with VCR alone, four samples treated with RA alone, and two samples treated with the combination of VCR and RA. The results suggest that treatment using VCR and ATRA may be effective in the differentiation therapy of AML.

Acute Disease↗