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Biomedical subjects

K F Wong

Publications and source records attributed to K F Wong.

At least 37 records · Page 2Linked to original sources
PubMed2003

Waldenström macroglobulinemia with a novel der(8;17)(q10;q10).

We report the occurrence of an unbalanced whole-arm translocation of der(8;17)(q10;q10) in an 80-year-old female patient with Waldenström macroglobulinemia. To our knowledge, der(8;17)(q10;q10) has not been described in Waldenström macroglobulinemia. Although this cytogenetic abnormality has been reported in a number of solid tumors, a literature review suggests also a possible association with B-cell chronic lymphoproliferative disorders.

Aged↗
PubMed2003

Diffuse large B-cell lymphoma with occult marrow involvement and a novel t(9;10)(q32;q22).

A 33-year-old man was found to have stage IV diffuse large cell lymphoma with visceral, cutaneous, and central nervous system involvement. Although examination of the posttreatment bone marrow failed to show morphologic evidence of lymphoma involvement, cytogenetic study of the marrow mononuclear cells showed the presence of a clonal abnormality t(9;10)(q32;q22), a hitherto undescribed chromosomal abnormality in diffuse large B-cell lymphoma.

Adult↗
PubMed2003

Major form of NUP98/HOXC11 fusion in adult AML with t(11;12)(p15;q13) translocation exhibits aberrant trans-regulatory activity.

Three adult patients with de novo acute myeloid leukemia of distinct subtypes harboring t(11;12)(p15;q13) have been investigated to characterize the genes involved in that translocation. Through molecular cytogenetics, a chromosome break was detected at the 3' part of nucleoporin 98 (NUP98) gene at 11p15. Using rapid amplification of cDNA end, we identified the partner gene at 12q13, HOXC11. Molecular analysis showed that exon 12 of NUP98 was fused in-frame to exon 2 of HOXC11 in all three cases with t(11;12)(p15;q13). Therefore, this type of fusion may represent the major form of the NUP98-HOXC11 chimera so far reported. Moreover, two out of three cases had a confirmed deletion of the 3' part of NUP98 gene and more telomeric region of 11p harboring a group of tumor-suppressor genes. Interestingly, the NUP98-HOXC11 protein when assayed in a GAL4 reporter system, showed an aberrant trans-regulatory activity as compared to the wild-type HOXC11 in both COS-7 and HL-60 cells. Therefore, NUP98-HOXC11 may contribute to the leukemogenesis by interfering with the cellular mechanism of transcriptional regulation.

Adult↗
PubMed2003

Consolidation therapy with autologous blood stem cell transplantation in a patient with primary plasma cell leukaemia.

Primary plasma cell leukaemia (PPCL) is a rare form of plasma cell dyscrasia. Conventional melphalan-based treatment is often ineffective, with a reported median survival of 2-7 months only. We report a 53-year-old man with PPCL who was treated with four cycles of combination chemotherapy including vincristine, adriamycin and dexamethasone that resulted in a good partial remission. High-dose melphalan 200 mg/m2 and autologous peripheral blood stem cell (PBSC) rescue was then given 6 months after diagnosis. Maintenance interferon-alpha was started 8 weeks after transplantation with good drug compliance. Complete remission was achieved and molecular remission was documented 11 months after autologous PBSC transplantation. In conclusion, high-dose therapy followed by autologous stem cell rescue is a feasible option for PPCL that can result in a reasonably sustained remission.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

A novel t(2;3)(q31;p13) in acute myelocytic leukemia.

We report a case of acute myelocytic leukemia without maturation exhibiting a novel t(2;3)(q31;p13). Conventional cytogenetics showed the concomitant occurrence of a single metaphase with 47,XX,+8. Nevertheless, interphase cytogenetics by fluorescence in situ hybridization using a chromosome 8 alpha-satellite DNA probe showed that the percentage of cells with three hybridization signals was within the control range.

Chromosomes, Human, Pair 2↗
PubMed2002

Hypoplastic myelodysplastic syndrome-a clinical, morphologic, or genetic diagnosis?

We report a middle-aged female with an 11-year history of nonprogressive pancytopenia and severely hypoplastic marrow with minimal morphologic dysplasia. A diagnosis of hypoplastic myelodysplastic syndrome (MDS) was made because of the finding of a persistent clonal abnormality, del(13)(q12q14), and the subsequent demonstration of a single Auer rod-containing blast in the peripheral blood smear. The case illustrates the problems in the differentiation between aplastic anemia and hypoplastic MDS.

Adult↗
PubMed2002

Precursor T-lymphoblastic leukemia with a novel t(1;22)(p34;q13).

A 37-year-old woman that presented with cervical lymphadenopathy and leukocytosis was found to have precursor T-lymphoblastic leukemia (T-ALL). Cytogenetic study of the leukemic cells showed a 46,XX, t(1;22)(p34;q13) karyotype. The t(1;22)(p34;q13) is a novel chromosomal abnormality in human malignancies and is probably a variant form of the t(1;14)(p34;q11) found in precursor T-ALL.

Adult↗
PubMed2002

Gain of chromosome 3/3q in B-cell chronic lymphoproliferative disorder is associated with plasmacytoid differentiation with or without IgM overproduction.

Trisomy 3 has been reported to be associated with marginal zone B-cell lymphoma. However, its occurrence and significance in other B-cell chronic lymphoproliferative disorders has not been fully defined. We report five cases of B-cell chronic lymphoproliferative disorders showing gain of chromosome 3 or 3q. The patients were elderly males who presented with splenomegaly with or without hepatomegaly and lymphadenopathy. The diagnoses included chronic lymphocytic leukemia (3 cases), prolymphocytic leukemia (1 case), and Waldenstrom macroglobulinemia (1 case). Distinctive feature in this group of patients was the plasmacytoid appearance of the leukemic lymphocytes, with an associated IgM hypergammaglobulinemia in three patients. The relationship between the gain of chromosome 3 and plasmacytoid differentiation in B-cell chronic lymphoproliferative disorders is discussed.

Aged↗
PubMed2002

Chronic lymphocytic leukemia with a novel der(8;15)(q10;q10) translocation.

A 71-year-old male was found to have chronic lymphocytic leukemia. Cytogenetic study of the leukemic lymphocytes shows a 46,XY,der(8;15)+15. The der(8;15) is a novel chromosomal abnormality in human malignancies. The resulting loss of 8p and trisomy 15q are both unusual chromosomal changes in chronic lymphocytic leukemia.

Aged↗
PubMed2002

Chromosomal abnormalities in T-cell large granular lymphocyte leukaemia: report of two cases and review of the literature.

Cytogenetic information on T-cell large granular lymphocyte leukaemia (T-LGL; large granular lymphocytosis) is limited. We report two cases of T-LGL with unusual karyotypic aberrations. The first case showed a novel inv(7)(p15q22) as the sole chromosomal abnormality, while the second case showed an inv(14)(q11q32) with evidence of clonal evolution. The breakpoints 7p14-p15 and 14q11 coincide with the T-cell receptor (TCR)-gamma and TCR-alpha/TCR-delta gene loci respectively. This is the first report describing the possible involvement of T-cell receptor genes in karyotypic aberrations in T-LGL.

Adult↗
PubMed2002

Atypical blasts and bone marrow necrosis associated with near-triploid relapse of acute promyelocytic leukemia after arsenic trioxide treatment.

The pathologic features of acute promyelocytic leukemia (APL) with t(15;17)(q22;q21) are highly characteristic, which with few exceptions enable a firm diagnosis to be made on morphologic grounds. An APL patient in first relapse presented with large, bizarre circulating blasts and bone marrow necrosis 2 weeks after chemotherapy consolidation for an arsenic trioxide-induced remission. Although a morphologic diagnosis could not be reached, cytogenetic investigations showed a near-triploid clone with t(15;17), confirming APL in second relapse. This case showed that clonal evolution with additional karyotypic aberrations might alter the blast morphology and pathologic features in APL.

Adult↗
PubMed2001

Cationic poly(ethyleneglycol) lipids incorporated into pre-formed vesicles enhance binding and uptake to BHK cells.

This paper describes a new method for enhancing the interaction of liposomes with cells. A novel class of cationic poly(ethyleneglycol) (PEG)-lipid (CPL) conjugates have been characterized for their ability to insert into pre-formed vesicles and enhance in vitro cellular binding and uptake of neutral and sterically-stabilized liposomes. The CPLs, which consist of a distearoylphosphatidylethanolamine (DSPE) anchor, a fluorescent dansyl moiety, a heterobifunctional PEG polymer (M(r) 3400), and a cationic headgroup composed of lysine derivatives, have been described previously [Bioconjug. Chem. 11 (2000) 433]. Five separate CPL, possessing 1-4 positive charges in the headgroup (referred to as CPL(1)-CPL(4), respectively), were incubated (as micellar solutions) in the presence of neutral or sterically-stabilized cationic large unilamellar vesicles (LUVs), and were found to insert into the external leaflet of the LUVs in a manner dependent on temperature, time, CPL/lipid ratio, and LUV composition. For CPL/lipid molar ratios < or =0.1, optimal insertion levels of approximately 70% of initial CPL were obtained following 3 h at 60 degrees C. The insertion of CPL resulted in aggregation of the LUVs, as assessed by fluorescence microscopy, which could be prevented by the presence of 40 mM Ca(2+). The effect of CPL-insertion on the binding of LUVs to cells was examined by fluorescence microscopy and quantified by measuring the ratio of rhodamine fluorescence to protein concentration. Neither control LUVs or LUVs containing CPL(2) displayed significant uptake by BHK cells. However, a 3-fold increase in binding was observed for LUVs possessing CPL(3), while for CPL(4)-LUVs values as high as 10-fold were achieved. Interestingly, the increase in lipid uptake did not correlate with total surface charge, but rather with increased positive charge density localized at the CPL distal headgroups. These results suggest that incorporation of CPLs into existing liposomal drug delivery systems may lead to significant improvements in intracellular delivery of therapeutic agents.

Animals↗
PubMed2001

Efficient encapsulation of antisense oligonucleotides in lipid vesicles using ionizable aminolipids: formation of novel small multilamellar vesicle structures.

Typical methods used for encapsulating antisense oligodeoxynucleotides (ODN) and plasmid DNA in lipid vesicles result in very low encapsulation efficiencies or employ cationic lipids that exhibit unfavorable pharmacokinetic and toxicity characteristics when administered intravenously. In this study, we describe and characterize a novel formulation process that utilizes an ionizable aminolipid (1,2-dioleoyl-3-dimethylammonium propane, DODAP) and an ethanol-containing buffer system for encapsulating large quantities (0.15--0.25 g ODN/g lipid) of polyanionic ODN in lipid vesicles. This process requires the presence of up to 40% ethanol (v/v) and initial formulation at acidic pH values where the DODAP is positively charged. In addition, the presence of a poly(ethylene glycol)-lipid was required during the formulation process to prevent aggregation. The 'stabilized antisense-lipid particles' (SALP) formed are stable on adjustment of the external pH to neutral pH values and the formulation process allows encapsulation efficiencies of up to 70%. ODN encapsulation was confirmed by nuclease protection assays and (31)P NMR measurements. Cryo-electron microscopy indicated that the final particles consisted of a mixed population of unilamellar and small multilamellar vesicles (80--140 nm diameter), the relative proportion of which was dependent on the initial ODN to lipid ratio. Finally, SALP exhibited significantly enhanced circulation lifetimes in mice relative to free antisense ODN, cationic lipid/ODN complexes and SALP prepared with quaternary aminolipids. Given the small particle sizes and improved encapsulation efficiency, ODN to lipid ratios, and circulation times of this formulation compared to others, we believe SALP represent a viable candidate for systemic applications involving nucleic acid therapeutics.

Animals↗
PubMed2001

Waldenström macroglobulinemia with karyotypic aberrations involving both homologous 6q.

An 84-year-old female presenting with proptosis and hyperviscosity syndrome was found to have Waldenström macroglobulinemia. Karyotypic analysis showed structural chromosomal abnormalities involving both homologous chromosomes 6 with a deleted 6q at q21-q23 and a complex three-break rearrangement in the t(6;13;21)?(q21;q14;q11). A literature review suggests that deletions of chromosome 6 at 6q21 are associated with lymphoplasmacytoid differentiation and IgM production in B-cell chronic lymphoproliferative disorders.

Aged↗
PubMed2001

Pathology of fatal human infection associated with avian influenza A H5N1 virus.

Eighteen cases of human influenza A H5N1 infection were identified in Hong Kong from May to December 1997. Two of the six fatal cases had undergone a full post-mortem which showed reactive hemophagocytic syndrome as the most prominent feature. Other findings included organizing diffuse alveolar damage with interstitial fibrosis, extensive hepatic central lobular necrosis, acute renal tubular necrosis and lymphoid depletion. Elevation of soluble interleukin-2 receptor, interleukin-6 and interferon-gamma was demonstrated in both patients, whereas secondary bacterial pneumonia was not observed. Virus detection using isolation, reverse transcription-polymerase chain reaction and immunostaining were all negative. It is postulated that in fatal human infections with this avian subtype, initial virus replication in the respiratory tract triggers hypercytokinemia complicated by the reactive hemophagocytic syndrome. These findings suggest that the pathogenesis of influenza A H5N1 infection might be different from that of the usual human subtypes H1-H3.

Adolescent↗