Myelodysplasia masquerading as parvovirus-related red cell aplasia with giant pronormoblasts.
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Aged↗
Biomedical subjects
T S Wan
Publications and source records attributed to T S Wan.
Transformation of diffuse large B-cell lymphoma into pre-B acute lymphoblastic leukemia: clinicopathologic features and clonal relationship.
A patient with fibrosing alveolitis developed a diffuse large B-cell (DLBC) lymphoma that expressed CD20 and CD30. After an initial response, the lymphoma relapsed and was salvaged with further chemotherapy. After another remission of 3 years, a pre-B-cell acute lymphoblastic leukemia (ALL), which expressed CD10, CD19, CD22, CD79a, CD34 and terminal deoxyribonucleotidyl transferase, developed and led to death. Molecular analysis of the immunoglobulin heavy-chain gene showed that the initial lymphoma and its relapse were clonally related. At leukemic relapse, 2 clones related to the initial and relapsed lymphoma clones were present. DLBC lymphomas arise from post-follicle center B cells, whereas ALL arises from pregerminal B cells. Therefore, a direct transformation of DLBC lymphoma to ALL appears unlikely. The overall features suggest instead separate lymphoma and leukemic evolution from a common mutated B-cell precursor rather than transformation of DLBC lymphoma to ALL.
Aged↗
Aberrant p15 gene promoter methylation in therapy-related myelodysplastic syndrome and acute myeloid leukaemia: clinicopathological and karyotypic associations.
Seventeen patients with therapy-related myelodysplastic syndrome/acute myeloid leukaemia (t-MDS/AML) were examined for aberrant p15 gene methylation by methylation-specific polymerase chain reaction. Ten patients (58%) showed p15 methylation, which was significantly related to monosomy/deletion of chromosome 7q, but not to antecedent chemotherapy, blast count, leukaemic evolution or survival. In three of six patients with marrow samples obtained prior to the diagnosis of t-MDS/AML, p15 methylation predated disease development by up to 2 years. Bone marrow transplantation led to the disappearance of p15 methylation in one patient. These results showed that p15 methylation was an early event in the evolution of some t-MDS/AML patients.
Acute Disease↗
Concurrent mediastinal B cell lymphoma and chronic myeloid leukemia with an unusually favorable response to chemotherapy.
A 67-year-old Chinese woman presented with mediastinal B cell lymphoma in 1992 with incidental leukocytosis. Bone marrow and peripheral blood findings confirmed the diagnosis of chronic myeloid leukemia (CML). After combination chemotherapy and radiotherapy for lymphoma, her peripheral blood counts remained normal, and she refused further treatment for nearly six years. Frank hematologic relapse occurred in 1998 and low dose hydroxyurea was used, which was stopped after six months owing to cytopenia. She remained well without treatment at 12-year follow up. Retrospective Southern blot analysis confirmed BCR gene rearrangement in marrow in 1992 and 1998, but not in the lymphoma or the latest peripheral blood. Fluorescence in-situ hybridzation analysis showed no Philadelphia chromosome positive (Ph+) cells in the peripheral blood at last (FISH) follow-up, but BCR/ABL remained detectable. The relevance of the concomitant occurrence of CML and lymphoma and the unusually favorable response of CML to chemotherapy to the pathogenesis of CML is discussed.
Aged↗
Tyrosine kinase inhibitor STI571 in the treatment of Philadelphia chromosome-positive leukaemia failing myeloablative stem cell transplantation.
Eight patients with Philadelphia chromosome-positive (Ph(+)) leukaemia relapsing from stem cell transplantation (SCT) (one syngeneic and seven allogeneic) were treated with the tyrosine kinase inhibitor STI571. Five patients relapsing as chronic myeloid leukaemia (CML) in chronic phase achieved a complete haematological response, with complete and major cytogenetic responses occurring in four and one cases, respectively. One patient became negative for BCR/ABL in the bone marrow. Three patients relapsed as acute leukaemia (two CML in myeloblastic crisis and one Ph(+) acute lymphoblastic leukaemia), all of whom achieved haematological and cytogenetic responses. One patient also became BCR/ABL negative. However, pancytopenia and graft-versus-host disease led to cessation of treatment in the remaining two cases, which was followed by disease recurrence refractory to further STI treatment. Our results showed that Ph(+) leukaemic relapses after SCT might respond well to STI571 therapy.
Adolescent↗
Subvalvular pulmonary stenosis, demyelination and myelodysplasia with monosomy 7.
We report a 23-year-old male with subvalvular pulmonary stenosis (PS) presenting with concurrent acute demyelinating neuropathy and myelodysplasia with monosomy 7. There was no stigmata of Noonan syndrome or neurofibromatosis, nor any family history of cardiac or hematologic disorders. There are 40 reported pediatric cases of Noonan syndrome with subvalvular PS that developed leukemia, over two-thirds with monosomy 7. There is also a genetic overlap between Noonan syndrome and neurofibromatosis, which is also closely associated with demyelination and leukemia. The importance of recognition of rare clinical syndromes that may predispose to leukemia is discussed.
Adult↗
Nonrandom chromosomal imbalances in human ovarian surface epithelial cells immortalized by HPV16-E6E7 viral oncogenes.
We had previously immortalized human ovarian surface epithelial (HOSE) cells using HPV16E6E7 ORFs. In order to identify crucial genetic events involved during cell immortalization, the genomic profile of immortalization of five HOSE cell lines was analyzed by comparative genomic hybridization. Our results showed that chromosomal imbalance was common in HOSE cells after immortalization. The common chromosomal imbalances identified in immortal HOSE cells are: +19q13.1 (5/5 lines), -13q12 approximately qter (4/5 lines), +5q15 approximately q33 (3/5 lines), +20q11.2 approximately q13.2 (3/5 lines) and -22q11.2 approximately qter (3/5 lines). Other chromosomal imbalances, which were detected in two of the five immortal HOSE cell lines, included gains on chromosome 1 and 11q12 approximately q13, and losses on 2p, 4q, 8p, 10p and 11q14 approximately qter. The chromosomal imbalances observed in HOSE cells before immortalization include -8pter approximately p11.2, -11q23 approximately qter, -13q12 approximately qter and +19 which may represent early genetic events during cell immortalization. The genomic profile was examined in one HOSE cell line (HOSE 6-3) at various stages of immortalization. The genomic profiles of HOSE 6-3 cells after crisis were largely stable. A few additional chromosomal imbalances were detected in the immortalized HOSE cells after an extensive culture period including +11pter approximately q23, -15q23 approximately qter, and +17q12 approximately qter. Identification of nonrandom chromosomal imbalance in immortalized HOSE cells may facilitate the identification of specific chromosomes harboring genes involved in the immortalization of human ovarian surface epithelial cells.
Cell Line↗
Derivative (1;18)(q10;q10): a recurrent and novel unbalanced translocation involving 1q in myeloid disorders.
We report two cases of hematological malignancies, comprising a case of myelodysplastic syndrome (MDS) that rapidly evolved into acute myeloid leukemia, and a case of myeloproliferative disorder (MPD), in which der(1;18)(q10;q10) was found as the sole acquired karyotypic abnormality. This observation indicates that the unbalanced translocation is a recurrent aberration in myeloid disorders. To the best of our knowledge, centromeric fusion between long arms of chromosomes 1 and 18, leading to a normal chromosome 18 substituted with a der(1;18) chromosome, is novel and has not been described in cancer. Mechanistically, either trisomy 1q or monosomy 18p that results from the translocation may potentially contribute to leukemogenesis. Finally, chromosomes with large constitutive heterochromatin bands such as chromosome 1 may be at risk of centromeric instability and be predisposed to centromeric fusion with other chromosomes.
Acute Disease↗
Analysis of corticosteroids in equine urine by liquid chromatography-mass spectrometry.
A liquid chromatography-mass spectrometry (LC-MS) method for the analysis of corticosteroids in equine urine was developed. Corticosteroid conjugates were hydrolysed with beta-glucuronidase; free and enzyme-released corticosteroids were then extracted from the samples with ethyl acetate followed by a base wash. The isolated corticosteroids were detected by LC-MS and confirmed by LC-MS-MS in the positive atmospheric pressure chemical ionisation mode. Twenty-three corticosteroids (comprising hydrocortisone, deoxycorticosterone and 21 synthetic corticosteroids), each at 5 ng/ml in urine, could easily be analysed in 10 min.
Adrenal Cortex Hormones↗
Establishment and characterization of a new xenograft-derived human esophageal squamous cell carcinoma cell line SLMT-1 of Chinese origin.
A new human esophageal cancer cell line, named SLMT-1, was established from a nude-mouse xenograft of a well-differentiated esophageal squamous cell carcinoma (ESCC) of the lower esophagus from a male Hong Kong Chinese patient. SLMT-1, passaged over 34 times and with a doubling time of 31 hours, has the microscopic features of epithelial cells with adherent growth as a monolayer. The general biologic properties of SLMT-1 cells were characterized by (1) a positive test of tumorigenicity obtained by injecting cells subcutaneously into athymic nude mice and observing their development into well-differentiated squamous cell carcinoma; (2) immunohistochemical staining using antibodies (AE1/AE3, CAM5.2 and MAK 6) which show the presence of cytokeratin intermediate filaments; and (3) electron microscopy demonstrating the morphologic features of epithelial cells with the presence of desmosomes. The cytogenetic abnormalities found in both the primary culture and SLMT-1 included der(1;14)(q10;q10), add(1)(p1?), +1, +2, del(3)(q11), +6, +7, i(8)(q10), +8, +10, +11, -13, -15, +16, +17, -18, -19, -Y and marker chromosomes. Additional changes observed in the 34th passage included gains as well as losses of both numerical and structural abnormalities. Comparative genomic hybridization (CGH) indicated copy number gains on chromosomal regions 3q32-qter, 5p, 8p12-p11.2, 11q13-q22 and 13q22-qter, and loss of the Y. The gains of 8p12-p11.2 in SLMT-1 cells are novel to ESCC. Based on its distinct and common characteristics, the SLMT-1 cell line serves as a useful tool for studying the molecular and genetic basis of the pathogenesis of ESCC.
Animals↗
Analyses of quaternary ammonium drugs in horse urine by capillary electrophoresis-mass spectrometry.
A capillary electrophoresis-mass spectrometry (CE-MS) method for the analysis of quaternary ammonium drugs in equine urine was developed. Quaternary ammonium drugs were first extracted from equine urine by ion-pair extraction and then analysed by CE-MS in the positive electrospray ionization (ESI) mode. Within 12 min, eight quaternary ammonium drugs, each at 1 ng/mL in horse urine, could be detected. The confirmation of these drugs in urine samples was achieved by capillary electrophoresis tandem mass spectrometry (CE-MS/MS). A direct comparison of this method was made with existing liquid chromatography/mass spectrometry (LC-MS) methods in the detection and confirmation of glycopyrrolate and ipratropium bromide in horse urine. While the two drugs could be detected within the same CE-MS run at 1 ng/mL in urine, they could only be detected in separate LC-MS runs at 5 ng/mL in urine. In addition, CE-MS consumed a much smaller volume of extract; the analyte peak widths, in some cases, were much narrower; and as the quaternary ammonium ions were well separated electrophoretically from the mainly neutral urine matrix, a much cleaner background in the CE-MS total ion trace was observed.
Animals↗
Cytogenetic biclonality in polycythemia vera: unusual and unrelated clones.
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Chromosome Aberrations↗
Late onset post-transplantation lymphoproliferative disease of recipient origin following cytogenetic relapse and occult autologous haematopoietic regeneration after allogeneic bone marrow transplantation for acute myeloid leukaemia.
A post-transplantation lymphoproliferative disease (PTLD) of recipient origin was identified in one of 376 consecutive cases of allogeneic bone marrow transplantation (BMT). This occurred in a 36-year-old woman who received an allogeneic BMT for acute myeloid leukaemia in relapse. At 15 months after BMT, recipient haematopietic and leukaemic cells were found in the bone marrow, which disappeared on withdrawal of immunosuppression. However, severe graft-versus-host disease (GVHD) necessitated the continuation of immunosuppression, leading to the occurrence of PTLD in the liver and lung 12 months afterwards. Fluorescence in situ hybridisation showed that the neoplastic cells were of recipient origin. Although the PTLD also responded completely to withdrawal of immunosuppression, the patient finally died from the complications of GVHD. This case of late onset PTLD post-BMT showed features similar to those in solid organ transplantation, in that the tumour was of recipient origin and responded well to the withdrawal of immunosuppression. Of further interest is that recipient lymphoid regeneration had accompanied autologous haematopoietic regeneration and become a target for subsequent neoplastic transformation.
Acute Disease↗
Characterization of additional genetic events in childhood acute lymphoblastic leukemia with TEL/AML1 gene fusion: a molecular cytogenetics study.
TEL/AML1 gene fusion that results from a cryptic t(12;21) is the most common genetic aberration in childhood B-lineage acute lymphoblastic leukemia (ALL). While the translocation may initiate the leukemic process, critical secondary genetic events are currently believed to be pivotal for leukemogenesis. We investigated 12 cases of childhood ALL with TEL/AML1 gene fusion by fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH) and documented additional or secondary genetic changes in seven patients (58%). Three patients showed extra copies of chromosome 21 including a case in which the trisomy 21 (+21) clone was distinct from the one harboring TEL/AML1 gene fusion. Interestingly, one patient without +21 showed amplification of the AML1 gene on chromosome 21q, supporting the contention that AML1 amplification may be an important additional genetic event. Gene expression study by semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) in two of these four patients showed an increase in AML1 transcripts that paralleled the increase in gene copy number. Deletion of the normal TEL allele was detected in two patients, with one of them showing loss of chromosome 12 together with duplication of the der(12)t(12;21). Finally, one patient showed duplication of the fusion signal. Our findings confirm that additional or secondary genetic changes including AML1 amplification are commonly encountered in childhood ALL with TEL/AML1 gene fusion, which are envisaged to play significant roles in disease progression.
Adolescent↗
Relationship between transient abnormal myelopoiesis and acute megakaryoblastic leukaemia in Down's syndrome.
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Child, Preschool↗
Philadelphia (Ph) chromosome-positive chronic myeloid leukaemia relapsing as Ph-negative leukaemia after allogeneic bone marrow transplantation.
Two patients with Philadelphia chromosome-positive (Ph(+)) chronic myeloid leukaemia (CML) relapsed 1.5 and 5 years after allogeneic bone marrow transplantation (BMT). Although the leukaemias were of recipient origin, t(9;22) could no longer be detected using conventional cytogenetics/fluorescence in situ hybridization or molecularly. Both patients responded to immunotherapy with donor lymphocytes/peripheral blood stem cells, although one patient ultimately relapsed again. These patients were similar to the occurrence of Ph(-) leukaemias previously described in Ph(+) CML after treatment with interferon or autologous BMT, and might be relevant in the pathogenesis and monitoring of treatment after BMT in CML.
Adult↗
Chiral analysis by electrospray ionization mass spectrometry/mass spectrometry. 1. Chiral recognition of 19 common amino acids.
Chiral recognition of 19 common amino acids was achieved by investigating the collision-induced dissociation spectra of protonated trimers that were formed from the electrospray ionization of amino acids in the presence of one of the following chiral selectors: L- or D-N-tert-butoxycarbonylphenylalanine, L- or D-N-tert-butoxycarbonylproline, and L- or D-N-tert-butoxycarbonyl-O-benzylserine. The protonated trimers were dissociated to protonated dimers, and the intensity ratios of the protonated dimer (product ion) to the protonated trimer (precursor ion), i.e., the observed dissociation efficiency, was found to be strongly dependent on the chirality of the amino acids with respect to that of the chiral selectors. The results showed that the chirality of all 19 common amino acids can be definitely differentiated. The method was demonstrated as rapid, sensitive, precise, robust, and requiring no reference standards and only minimal sample preparation. The chirality of all three amino acids in a mixture was determined without prior separation of the amino acids, consuming only 70 pmol of sample and requiring only approximately 14 min of mass spectrometric measurements. A cyclodipeptide with unknown chirality was determined to be cyclo-(L-Pro-L-Leu) by acid hydrolysis followed by the present method, and the results were consistent with the physiochemical properties and NMR data of the compound. This study suggested that ESI-MS/MS can be a promising approach for the chiral recognition of other compounds.
Algorithms↗
Chiral analysis by electrospray ionization mass spectrometry/mass spectrometry. 2. Determination of enantiomeric excess of amino acids.
The determination of enantiomeric excess (ee) of amino acids was achieved by investigating the collision-induced dissociation spectra of protonated trimers that were formed by electrospray ionization of amino acids in the presence of one of the following chiral selectors: L- or D-N-tert-butoxycarbonylphenylalanine, L- or D-N-tert-butoxycarbonylproline, and L- or D-N-tert-butoxycarbonyl-O-benzylserine. The protonated trimers were dissociated to form protonated dimers, and the observed dissociation efficiency r (i.e., the intensity ratio of protonated dimers to protonated trimers) for an enantiomeric mixture was found to be related to its ee value by the following equation: r = a + b/(c + ee), where a, b, and c were constants. A linear calibration plot was obtained by plotting r versus 1/(c + ee), where c was calculated with the MATLAB software, or by plotting 1/(r - r0) versus 1/ee, where r0 was the r value for the racemic mixture. The latter "two-reciprocal" method was more convenient for application. Another practical method for ee determination was the "three-point" method, whereby the ee of an unknown sample with a measured r value could be derived from the equation ee = 100¿1/(rL - r0) - 1/(rD - r0)¿/¿2/(r - r0) - 1/(rL - r0) - 1/(rD - r0)¿, with rL and rD being the r values for the enantiomerically pure L- and D-forms of the sample, respectively. A calibration plot was not required. The ee determination was achieved with acceptable precision even for the worst case of acceptable chiral recognition with a particular chiral selector, suggesting that the ee determination of all 19 common amino acids could be achieved by the present method. The ee of a histidine sample was determined both by the two-reciprocal method, giving an error of 0.2% ee (1.1% relative error) and consuming only approximately 5.3 nmol of sample, and by the three-point method, giving an error of 0.4% ee and consuming only approximately 2.3 nmol of sample. In the latter case, it took 27 min for the mass spectrometric measurements of the three calibration standards and an additional 9 min for the unknown sample. The direct ee determination of more than one amino acid in a mixture was also demonstrated in the study.
Amino Acids↗