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S K Ma

Publications and source records attributed to S K Ma.

At least 73 records · Page 4Linked to original sources
PubMed2001

Clinical phenotype of triplicated alpha-globin genes and heterozygosity for beta0-thalassemia in Chinese subjects.

The presence of extra copies of alpha-globin gene has been shown to worsen the degree of anemia in beta-thalassemia heterozygotes. We describe the clinical phenotype of eight Chinese subjects with heterozygosity for both triplicated alpha-globin gene and a beta0-thalassemia allele. They were identified through genotyping of beta-thalassemia intermedia and major patients, and through community-based thalassemia screening program in Hong Kong. Standard molecular techniques were used in the determination of genotype. All subjects in this series showed five copies of alpha-globin genes (alphaalphaalpha/alphaalpha) in association with a beta0-thalassemia allele. Although genotypically identical, six subjects showed a beta-thalassemia intermedia phenotype while two were clinically indistinguishable from beta-thalassemia minor, implying the presence of genetic modifying factors that remained undefined. Triplication of alpha-globin gene and heterozygosity for beta0-thalassemia accounted for 15% of beta-thalassemia intermedia patients at our locality and was associated with a mild clinical phenotype. This genotype was not found among beta-thalassemia major patients. They presented in adulthood and were usually not transfusion dependent. When compared with simple beta-thalassemia heterozygotes, they showed obvious red cell abnormalities (hypochromasia, anisopoikilocytosis, circulating normoblasts), lower hemoglobin (Hb) and higher HbF levels. The presence of triplicated alpha-globin genes should always be considered in apparent beta-thalassemia carriers who were more symptomatic than expected, so that unnecessary investigations for the cause of anemia could be avoided. Finally, triplication of alpha-globin genes should be looked for in families with children affected by beta-thalassemia intermedia in which only one parent showed a picture of beta-thalassemia on Hb analysis.

Adolescent↗
PubMed2000

Complex cytogenetic abnormalities in T-lymphoblastic lymphoma: resolution by spectral karyotyping.

We describe a case of T-lymphoblastic lymphoma (T-LBL) in a 13-year-old boy in which conventional cytogenetic analysis of lymph node tissue showed complex karyotypic aberrations including add(1p), add(2q), and multiple chromosomal deletions involving 5q, 7p, 7q, 13q, and 16q. Analysis by spectral karyotyping (SKY) refined add(1p) to a paracentric inversion of 1p, and add(2q) to an unbalanced translocation between chromosomes 2 and 4. The chromosomal deletions were simple deletions except del(5q), which was confirmed by SKY to be a cryptic unbalanced translocation between chromosomes 5 and 18. The present report illustrates that SKY technology is useful in identifying subtle translocations and resolving complex karyotypic aberrations in neoplastic disorders.

Adolescent↗
PubMed2000

Familial acute myeloid leukemia with monosomy 7: late onset and involvement of a multipotential progenitor cell.

Familial acute myeloid leukemia (AML) with monosomy 7 is a rare syndrome with fewer than 10 families reported. The salient features included a young median age (8 years) at presentation, equal sex preference, and occurrence of cytopenias and myelodysplasia in nonleukemic family members. Owing to its rarity and the fact that many cases were reported quite some time ago, detailed clinicopathologic features of familial monosomy 7 were not available. We describe a family with three siblings affected by AML in whom monosomy 7 was demonstrated. This family showed several unique features, including the late onset of AML (at 34 and 37 years of age in two siblings), and the presence of an antecedent myelodysplastic phase before leukemia development. With fluorescence in situ hybridization, the monosomy 7 clone was shown to be capable of partial maturation, which was consistent with the biologic behavior of myelodysplasia. These observations suggest that familial leukemia with monosomy 7 is probably a multistep leukemogenic process in which monosomy 7 might be but one of the critical steps. Finally, the prognosis in these cases was poor, suggesting that more aggressive therapy may be needed to improve treatment outcome.

Adolescent↗
PubMed2000

beta-thalassemia intermedia caused by compound heterozygosity for Hb Malay (beta codon 19 AAC-->AGC; asn-->Ser) and codons 41/42 (-CTTT) beta(0)-thalassemia mutation.

We report a case of beta-thalassemia intermedia caused by compound heterozygosity for hemoglobin (Hb) Malay and codon 41/42 (-CTTT) beta(0)-thalassemia mutation in a 38-year-old Chinese woman. This patient has long-standing anemia with a baseline Hb level of around 70 g/L. She worked as a full-time cashier and had not required regular blood transfusions. Nevertheless, she had splenomegaly necessitating splenectomy, cholelithiasis, and iron overload. This case illustrates the varied phenotypic expression associated with compound heterozygosity for Hb Malay and other beta-thalassemia mutations. Since Hb Malay migrates as Hb A on electrophoresis and chromatography, this variant Hb mutation ought to be included in the differential diagnosis for beta-thalassemia major or intermedia patients of Southeast Asian descent who are reported to have Hb A on the basis of Hb analysis. The possible presence of this mutation should also be considered in appropriate cases for genetic counseling in couples at risk of conceiving fetuses with beta-thalassemia major or intermedia.

Adult↗
PubMed2000

Hairy cell leukemia in Hong Kong Chinese: a 12-year retrospective survey.

BACKGROUND: Hairy cell leukemia (HCL) is a unique chronic B cell lymphoproliferative disease (B-LPD), with distinct clinical and pathological features, and excellent treatment response to 2-chlorodeoxyadenosine (2-CDA) and pentostatin. There have been few reports of HCL from oriental countries. PATIENTS AND METHODS: A retrospective survey of HCL in six major hematology units in Hong Kong over a 12-year period. RESULTS: There were 18 cases of HCL identified. Most patients presented with fever, splenomegaly and monocytopenia. Lymphadenopathy was present in three patients, and open biopsy revealed tuberculosis infection in two cases. Seven cases received interferon and 12 cases received 2-CDA. Four patients died from bronchogenic carcinoma, cerebral vascular accident, fulminant hepatitis B virus reactivation and malignant melanoma. The remaining 14 patients are in clinical remission at a median of 6 years' follow-up; two are also surviving from second malignancies (thyroid papillary carcinoma and renal cell carcinoma). CONCLUSIONS: Parallel to the low incidence of B-LPD in Chinese, the incidence of HCL (0.035/100000 population per year) is much lower than in Western series. Other clinical features such as male dominance, clinical presentation, response to 2-CDA treatment, and association with second malignancy are similar to Western reports. However, two common complications in the Chinese population are the fulminant reactivation of hepatitis B infection and disseminated tuberculosis infection.

Adult↗
PubMed2000

Molecular characterization of der(15)t(11;15) as a secondary cytogenetic abnormality in acute promyelocytic leukemia with cryptic PML-RAR alpha fusion on 17q.

A case of acute promyelocytic leukemia (APL) with cryptic PML-RAR alpha fusion on 17q and add(15p) as a secondary abnormality was characterized using molecular cytogenetic techniques. Spectral karyotyping (SKY) showed that chromosome 11 material was added to 15p, forming a der(15)t(11;15), which was refined to der(15)t(11;15)(q13.2;p13) with information obtained by comparative genomic hybridization (CGH). Interstitial insertion of chromosome 15 material into chromosome 17q was found by fluorescence in situ hybridization (FISH) with whole chromosome painting (WCP) probes. This study illustrates the necessity of a combination of molecular cytogenetics to decipher complex karyotypic abnormalities and cryptic translocations in leukemia.

Chromosomes, Human, Pair 11↗
PubMed2000

Analysis of MLL-derived transcripts in infant acute monocytic leukemia with a complex translocation (1;11;4)(q21;q23;p16).

It has been proposed, on the basis of cytogenetic studies and molecular analysis of MLL-derived transcripts in acute leukemia with 11q23 rearrangement, that only one fusion gene transcript present on the der(11) chromosome is critical for leukemogenesis. This view is challenged by a recent observation in a case of leukemia with a complex translocation that results in MLL being fused in-frame to two different partner genes. We investigated a case of infant monocytic leukemia with a complex translocation, (1;11;4)(q21;q23;p16). Molecular studies revealed MLL rearrangement by both fluorescence in situ hybridization and Southern blot analysis, and MLL/AF1q, but not the reciprocal message (i.e., AF1q/MLL), was amplified by polymerase chain reaction. Sequence analysis of MLL/AF1q revealed an in-frame fusion between MLL exon 6 and the breakpoint located six bases upstream of the ATG start site for AF1q. Our data suggest that only one form of MLL fusion gene is implicated in leukemogenesis in our case to t(1;11;4).

Base Sequence↗
PubMed2000

Cytogenetic characterization of childhood hepatoblastoma.

We describe the cytogenetic abnormalities in two cases of childhood hepatoblastoma. The first case was of fetal histology with squamous metaplasia, and cytogenetic study showed an add(5)(q31). Although an association between hepatoblastoma and familial adenomatous polyposis is recognized, the breakpoint in this case is distal to 5q21 and most probably does not involve the APC gene at that location. The second case was of macrotrabecular histology, and cytogenetic study showed an unbalanced translocation in the form of der(4)t(1;4)(q12;q34) in a hyperdiploid clone. Including our case, der(4)t(1;4)(q12;q34) has been recognized in four cases of hepatoblastoma, and it may be the first recurrent translocation in this tumor. Understanding the molecular mechanism and clinical significance of this translocation awaits analysis of more cases.

Child, Preschool↗
PubMed2000

Graft-versus-host disease after liver transplantation: documentation by fluorescent in situ hybridisation and human leucocyte antigen typing.

Graft-versus-host disease (GVHD) after liver transplantation is uncommon and the outcome is often fatal. A firm diagnosis of GVHD is difficult because the clinical triad of skin rash, marrow failure and diarrhoea can be indistinguishable from drug reaction or viral infection, and the presence of donor lymphocyte chimerism is not specific. We describe a case of severe GVHD in a female patient after liver transplantation from a male cadaveric donor. Skin biopsy showed characteristic changes of GVHD. Using Y-chromosome-specific fluorescent in situ hybridisation (FISH), male lymphocytes were demonstrated in 10% of marrow cells and in 90% of lymphocytes infiltrating the dermal epidermal junction. Donor human leucocyte antigens (HLAs) were detected in the peripheral blood, buccal mucosa and skin by polymerase chain reaction. The GVHD subsided with steroid and anti-thymocyte globulin, but recurred on tailing off of treatment. Despite maximum supportive therapy, including random donor leucocyte infusion, and marrow infusion from a HLA-identical sibling, the patient succumbed to sepsis. Our results showed the utility of combining morphological features with molecular techniques using FISH and HLA typing in confirming a diagnosis of GVHD.

Adult↗