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Biomedical subjects

Kit-Fai Wong

Publications and source records attributed to Kit-Fai Wong.

9 recordsLinked to original sources
PubMed2005

Serial studies of methylation of CDKN2B and CDKN2A in relapsed acute promyelocytic leukaemia treated with arsenic trioxide.

Ninety consecutive patients with acute promyelocytic leukaemia were investigated for promoter methylation of CDKN2B (alias p15) and CDKN2A (alias p16) in disease relapse and progression. CDKN2B methylation was significantly more frequent at first relapse (30/36, 83%) than at presentation (48/77, 62%) (P=0.025), while CDKN2A methylation appeared unaffected. Both acquisition and loss of CDKN2B methylation happened at relapse, with acquisition more frequent. No significant increase in CDKN2B and CDKN2A methylation occurred at more advanced relapses. At first or subsequent relapses, owing to highly effective salvage by arsenic trioxide, CDKN2B methylation did not impact on event-free survival or overall survival.

Antineoplastic Agents↗
PubMed2003

Natural killer cell neoplasms: a distinctive group of highly aggressive lymphomas/leukemias.

Natural killer (NK) cell neoplasms, which include extranodal NK/T-cell lymphoma (nasal and extranasal) and aggressive NK cell leukemia, are generally rare, but they are more common in people of Oriental, Mexican and South American descent. These neoplasms are highly aggressive, and show a strong association with Epstein-Barr virus. Extranodal NK/T-cell lymphoma most commonly affects the nasal cavity and other mucosal sites of the upper aerodigestive tract. Patients present with nasal obstruction or midfacial destruction. Despite the early stage of disease at presentation, overall survival is poor. Patients with the extranasal form of the lymphoma often present with high-stage disease, commonly involving the skin, gastrointestinal tract, testis, and soft tissue, and the prognosis is even worse. Histologically, the lymphoma can show a broad cytologic spectrum, but apoptosis, necrosis, and angioinvasion are common. The most common immunophenotype is CD2(+), surface CD3(-), cytoplasmic CD3(+), CD56(+). Based on currently available data, treatment of nasal NK/T-cell lymphoma should consist of radiotherapy, with or without multiagent chemotherapy. More research is required to ascertain the role of high-dose chemotherapy with stem cell rescue and that of non-multidrug resistance-related chemotherapeutic agents. Aggressive NK cell leukemia affects younger patients, who present with poor general condition, fever, and disseminated disease; they often die within a short time from systemic disease or complications such as multi-organ failure. The peripheral blood and bone marrow show atypical large granular lymphocytes, which exhibit an immunophenotype similar to that of extranodal NK/T-cell lymphoma. Aggressive NK cell leukemia must be distinguished from T-cell large granular lymphocyte leukemia and indolent NK cell lymphoproliferative disorder, both of which are indolent.

Diagnosis, Differential↗
PubMed2002

Specific patterns of gene methylation in natural killer cell lymphomas : p73 is consistently involved.

Aberrant methylation of promoter CpG regions is a putative mechanism whereby tumor suppressor genes are inactivated. We used a candidate gene approach to investigate the patterns and significance of this epigenetic change in natural killer (NK) cell malignancies. Thirty-three patients were studied for promoter methylation in five putative tumor suppressor genes by methylation-specific polymerase chain reaction (MSP), which has a sensitivity of 10(-3). The p73 gene was methylated in 94% of cases, a frequency that is the highest known for any human malignancy. In the NK cell lymphoma line NK92, p73 was also completely methylated, and the p73 transcript was correspondingly not detectable by quantitative polymerase chain reaction. Treatment of the cell line with 5-azacytidine, a demethylation reagent, led to demethylation of the p73 promoter and reinduction of p73 gene expression. These results suggested that promoter CpG methylation might be an important mechanism in suppressing p73 gene expression in NK cells. Other methylated genes included hMLH1 (63%), p16 (63%), p15 (48%), and RAR beta (47%). Methylation of two or more genes occurred in 88% of cases. With promoter methylation as a molecular marker, MSP identified two cases of occult marrow metastasis. Interestingly, the primary tumor and metastasis showed different methylation patterns, implying that separate clonal evolutions might have occurred at these sites. Furthermore, MSP also identified tumor infiltration in random oropharyngeal biopsies in a case where histological examination could not show evidence of tumor involvement. We conclude that NK cell malignancies show a specific pattern of promoter methylation, with p73 being consistently involved. These results suggest that p73 may be an important target in the neoplastic transformation of NK cells, and the demonstration of its methylation may serve as a potential molecular tool for NK cell lymphoma detection.

Adult↗