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Biomedical subjects

H F Tien

Publications and source records attributed to H F Tien.

At least 19 recordsLinked to original sources

Cytogenetic study of acute lymphoblastic leukemia and its correlation with immunophenotype and genotype.

Among 72 Chinese patients with acute lymphoblastic leukemia (ALL), 50 had clonal chromosomal abnormalities. Structural abnormalities were detected in 42 patients: these included t(9;22) in 9, t(1;19) in 6, t(4;11) in 5, del(11)(q23) in 4, and del(6q) in 4. Adults had a higher incidence of t(9;22) and t(1;19) but a lower incidence of t(4;11) and hyperdiploid greater than 50 karyotype than children. A significant difference was also noted in white blood cell (WBC) count among various karyotypic groups. Patients with chromosomal abnormalities t(9;22), t(1;19), t(4;11) and del(11) (q23) had a shorter complete remission duration as compared with patients free of these abnormalities. Immunophenotyping was performed on 69 patients. All patients with t(9;22), t(1;19), and t(4;11) had B-lineage ALL restricted to certain stages of maturation: groups III and IV, groups IV and V, and group II, respectively (according to the classification of Foon and Tood). Among patients with t(9;22), t(4;11), and del(11)(q23), which have been considered to be associated with acute mixed-lineage leukemia, one each, respectively, showed myeloid antigen expression on the leukemic blasts (My+ ALL). No cross-lineage rearrangements of immunoglobulin (Ig) or T-cell receptor (TCR) genes were detected in these karyotypic subgroups of patients who underwent gene analysis.

Adolescent

Cutaneous angiocentric T-cell lymphoma associated with Epstein-Barr virus.

BACKGROUND: Two unusual cases of cutaneous angiocentric T-cell lymphoma were found to be associated with Epstein-Barr virus infection. OBJECTIVE: The objective was to study the clinical course and the response of the disease to conventional chemotherapy. METHODS: Histologic specimens from both patients were studied. Clonal proliferation was assessed by Southern blot hybridization. RESULTS: The disease in both patients was rapidly progressive and responded poorly to aggressive treatment. Biopsy specimens showed infiltration of atypical lymphoid cells with angiocentricity and angiodestruction, which probably resulted in the observed tissue necrosis. Clonal proliferation of Epstein-Barr virus DNA was detected in tissue from primary skin lesions and disseminated nasal lesions. CONCLUSION: Epstein-Barr virus-associated angiocentric T-cell lymphoma in our patients was characterized by an aggressive course and resistance to conventional chemotherapy. A search for Epstein-Barr virus and the human T-lymphotropic virus should be performed in patients with atypical features of cutaneous T-cell lymphoma.

Adult

Inactivation of the retinoblastoma gene in acute myelogenous leukaemia.

To investigate the role of retinoblastoma susceptibility (RB) gene inactivation in leukaemogenesis, we evaluated 36 bone marrow specimens of acute leukaemia for RB protein expression by immunoprecipitation and Western blot analysis. 15 patients had no detectable RB protein at initial screening. However, nine of them were subsequently excluded due to evidence of protein degradation. Of 27 valid cases, six (22%) were repeatedly shown to lack expression of the RB protein with three different anti-RB antibodies. Five were patients with acute myelogenous leukaemia (AML) and one, mixed-lineage acute leukaemia. The RB inactivation was noted more frequently in AML (5/18, 28%) than in acute lymphoid leukaemia (0/7, 0%). By karyotyping, none of these six patients exhibited cytogenetic changes involving chromosome 13q14, the RB locus. There is no correlation between inactivation of the RB gene and FAB subtypes or cytogenetic changes. Four patients achieved complete remission with standard chemotherapy for 6, 12, 20 and 26+ months, respectively. Southern and Northern blot analyses further indicated that the RB genes were grossly intact and the level of RB transcripts did not decrease in the majority of these six patients. These results suggest that the absence of RB products in some of acute leukaemia might be regulated at the post-transcriptional level, and it imposes no significant effect on treatment response and prognosis.

Adolescent

Characterization of Philadelphia-chromosome-positive acute leukemia by clinical, immunocytochemical, and gene analysis.

Philadelphia chromosome (Ph') was detected at presentation in 10 out of 110 patients with acute lymphoblastic leukemia (ALL) and five of 168 patients with acute myelogenous leukemia (AML). Two other ALL patients who had studies at relapse were also included in the analyses. One of the 12 Ph'-positive (Ph+) ALL patients had simultaneous expression of myeloid-associated antigen on the leukemic blasts, while all the five AML patients coexpressed markers of lymphoid cells. Double labeling of the cells with myeloperoxidase and CD10 on three Ph+ AML cases showed that most leukemic blasts expressed either myeloperoxidase activity or CD10 but not both. Cross-lineage gene rearrangements of T-cell receptor (TCR) beta-chain gene were detected in three of the eight Ph+ ALL patients tested. All the four Ph+ AML cases studied showed immunoglobulin heavy chain gene rearrangements, and three of them also had simultaneous rearrangements of TCR beta-chain gene. The results revealed that Ph+ acute leukemia in this study belonged either to ALL or mixed lineage leukemia, and none was pure AML. This finding is contrary to that of acute blast crisis of chronic myelogenous leukemia in which the majority of patients had myeloid transformation. Rearrangements of bcr were detected in four of the 10 Ph+ ALL and three of the four Ph+ AML patients tested. No significant difference was noted in the clinical or hematologic manifestations among Ph+ leukemia with or without bcr rearrangements.

Adult

Immunoglobulin and T-cell receptor gene rearrangements in acute lymphoblastic leukemia--a higher incidence of double rearrangements in patients with myeloid antigen expression.

Among 160 patients who were diagnosed as having acute lymphoblastic leukemia (ALL) by French American British (FAB) criteria, 32 patients (20%) expressed myeloid-associated antigens on leukemic blasts (My+ALL). Correlation of immunophenotype with rearrangement of immunoglobulin (Ig) heavy chain and T-cell receptor (TCR) beta chain genes was performed on 73 of these patients (21 were My+ALL). Rearrangements of both Ig and TCR genes (double rearrangements) were detected in 24 patients, including three (19%) of 16 T-lineage ALL. 17 (33%) of 52 B-lineage ALL, and four of five ALL expressing both B and T-cell surface markers. Also a higher incidence of double rearrangements in My+ALL was found as compared with My-ALL (43% vs 29%). This difference was more evident when only B-lineage ALL was considered (50% in My+ patients vs 24% in My- patients). However the difference is not statistically significant yet possibly due to the small number of patients in the study. Further studies on more patients are needed to confirm this. In My-B-lineage ALL, rearrangements of TCR beta chain gene were restricted to certain subgroups (Groups III & IV) of patients who expressed CD10 surface antigens but lacked cytoplasmic Ig. In My+ B-lineage ALL, rearrangements of TCR beta chain gene could be found in various subgroups studied (Groups II through V). Cross-lineage gene rearrangement in My+ALL may involve mechanisms different from those in My-ALL.

Adolescent

A subset of acute lymphoblastic leukemia with co-expression of myeloid antigens: prevalence and clinical significance.

In order to evaluate the biological features and clinical significance of myeloid antigen expression in acute lymphoblastic leukemia (ALL), immunophenotype analysis was performed on leukemic cells from 160 patients diagnosed as ALL by the French, American and British (FAB) criteria using a comprehensive panel of monoclonal antibodies to lymphoid and myeloid associated antigens. Expression of myeloid antigens was found in 32 cases (20%), including 11 out of 49 adults (22.4%) and 21 out of 111 children (18.9%). CD33 was positive in 18 patients (11.3% of the total cases), CD13 in 15 patients (9.4%), CD 11b in 12 patients (7.5%) and CD14 in 1 patient (0.6%). Nine patients expressed two or more myeloid antigens. There were no significant differences in clinical manifestations and hematological pictures between the ALL patients with myeloid antigen expression (My+ ALL) and those without (My- ALL). No consistent chromosomal abnormality was found in My+ ALL. Eighty percent of the childhood and 44.4% of the adult My+ ALL patients achieved complete remission, compared with 87% and 80%, respectively, for childhood and adult My- ALL, but the differences were not statistically significant. After a median follow-up of 2.1 years, there were also no statistically significant associations between myeloid antigen expression and shorter duration of remission or poorer survival rate for patients with both adult and childhood ALL.

Adult

Epstein-Barr virus-associated peripheral T-cell lymphoma of activated CD8 phenotype.

Two childhood cases are reported of peripheral T-cell lymphoma; the neoplastic cells expressed activated CD8 (T8) phenotype and contained Epstein-Barr viral (EBV) DNA. Both patients had an aggressive and rapid clinical course despite chemotherapy. Elevated titers of antibodies to EBV-viral capsid antigen (greater than 640) and early antigen (greater than 10) were found in both patients. Histology revealed pleomorphic immunoblastic lymphoma with extensive necrosis in one case and an angioimmunoblastic lymphadenopathy-like pattern containing Reed-Sternberg-like giant cells in the other. Southern blot hybridization studies showed clonal rearrangement of the T-cell-receptor beta gene in both cases, and a cytogenetic study on one case revealed clonal structure abnormality involving chromosomes 1, 6, 7, 10, and 19. Analysis of the tumor DNA showed a high copy number of EBV genome per cell compared with that of Raji and Marmoset B 95.8 lines; the study for human T-cell leukemia virus type I was negative. The EBV genome was found by in situ hybridization in the tumor nuclei in both cases. In addition to Burkitt's lymphoma, T-cell lymphoma of the helper phenotype, and Hodgkin's disease, EBV can contribute to the development of CD8-positive aggressive T-cell lymphoma.

Adolescent

Deletion of the human retinoblastoma gene in primary leukemias.

As an initial step in evaluating the role of tumor suppressor genes in leukemogenesis, we surveyed primary leukemia cells from 130 patients for possible deletion of the retinoblastoma susceptibility (Rb) gene by Southern blot analysis. Two of them clearly showed homozygous deletion of Rb alleles. The first patient was a pre-B acute lymphoid leukemia (ALL) associated with a cytogenetic translocation: t(14;16)(q24;q22). The deletion was located at the 3' portion of the Rb gene, very close to the site of Rb gene deletion recently identified in an ALL cell line. The absence of Rb110 protein was further confirmed by Western blot analysis. The second patient was a chronic myelomonocytic leukemia (CMMoL), terminated in acute blastic transformation. Deletion of the 5' portion of Rb gene was found in leukemic cells in the chronic stage. The results indicated that inactivation of the Rb gene occurred in certain cases of leukemia. Its significance warrants further study.

Aged

Cytogenetic characterization of a nasopharyngeal carcinoma cell line and its subline.

Cytogenetic results of a nasopharyngeal carcinoma (NPC) cell line NPC-TW039 and its subline NPC-TW039-N1, established from the nude mouse transplant, were reported. This is the third case of NPC presented with banded karyotype, to date, in the literature. A 3q + marker chromosome, with involvement of band q25 similar to that present in the two previously reported cases, was detected in most tumor cells from both cell lines. The structural chromosome abnormalities of NPC-TW039-N1 were similar to its original cell line, NPC-TW039, except that the subline lost one marker chromosome and gained a new one.

Chromosome Aberrations

bcr rearrangements in Philadelphia chromosome-positive acute lymphoblastic leukemia. A study of five Chinese patients in Taiwan.

Cytogenetic studies were successfully conducted on 73 Chinese patients with acute lymphoblastic leukemia (ALL). A Philadelphia chromosome (Ph) was identified in four (9%) of the 46 children and in four (15%) of the 27 adults. None of these patients had any clinical features suggestive of chronic myelogenous leukemia (CML). Leukemic cells from five of the eight Ph-positive (Ph+) ALL patients were analyzed for bcr rearrangement by Southern blot analysis with three restriction enzymes and two bcr probes. One of the three children and both adult patients studied showed bcr rearrangement. Based on the data from the literature and the present study, 58% of adult and 14% of childhood Ph+ ALL patients demonstrated bcr rearrangement. There were no significant differences in clinical or laboratory findings between the two groups of patients with or without bcr rearrangement. Patients who had Ph+ ALL but no bcr rearrangement appear to have been victims of de novo acute leukemia, but it was still difficult to determine whether patients with bcr rearrangement had acute lymphoid transformation of subclinical CML. More studies and longer follow-ups are needed for clarification.

Adolescent

Infant leukemia: an analysis of nine Chinese patients.

A study was made of the cellular and molecular characteristics of nine Chinese infants, consecutively presenting with acute leukemia. Five cases were acute lymphoblastic leukemia (ALL); four were acute nonlymphoblastic leukemia (ANLL). Hyperleukocytosis, hepatosplenomegaly, and poor response to conventional therapy were common features, and CNS involvement was detected at diagnosis in three cases. The blast cells from all five cases with ALL expressed early B-cell markers, i.e., HLA-DR+, CD19+, but CD10-. Terminal deoxynucleotidyl transferase (TdT) was present in blasts from four of the five cases and periodic acid-Schiff staining in blasts from two patients only. The leukemic cells of one patient also showed positive nonspecific esterase activity and expressed myeloid-associated antigens CD33 (My9), CD11 (OkM1), and CD14 (My4 and Mo2). Molecular analysis of leukemic cell DNA from this and two other patients showed rearrangement of the immunoglobulin (Ig) heavy-chain genes, but without any evidence of kappa light-chain gene rearrangement. T-cell receptor (TCR) genes remained in the germline configuration in these cases. Cytogenetic analysis showed translocation t(4;11) (q21;q23) in all four cases studied. In the group of ANLL, three cases belonged to the M4 and one to the M2 subtype. Chromosomal abnormality involving 11q23 was also detected in two patients: t(11;17)(q23;q11) and del(11)(q14q23) in each case respectively. Neither Ig nor TCR gene rearrangement was present in blast cells from patients with ANLL. The data indicate that chromosomal rearrangement of band 11q23 was quite common in Chinese infants with either form of leukemia, a finding that may have pathogenetic implications.

Antigens, CD

A subset of acute nonlymphocytic leukemia with expression of surface antigen CD7--morphologic, cytochemical, immunocytochemical and T cell receptor gene analysis on 13 patients.

An increasing number of acute leukemias coexpressed markers normally believed to be restricted to a single lineage have been found recently. This special subgroup of leukemias have drawn a lot of attention because of their biologic and clinical significance. In a study of 100 consecutive de novo ANLL patients diagnosed by FAB criteria, T-cell antigen CD7 was identified on the leukemic blasts of 13 patients, ten of whom had M1 subtype of leukemia, myeloblastic leukemia without maturation. All the patients showed positive staining with myeloperoxidase and expressed myeloid markers CD13 and/or CD33, but lacked CD11b, a marker of more mature myeloid cells. Combined staining with myeloperoxidase and CD7 of the cells from four patients revealed coexpression of both markers on the same cells. None of the patients expressed the two other T-cell antigens CD2 or CD5. All ten patients who had DNA analysis showed germline configuration of TCR beta and gamma chain genes. One patient had chromosomal translocation involving 11q23, t(11; 19) (q23; p13), which is the site frequently associated with both myeloid and lymphoid malignancies. The clinical implications of this subgroup of patients need further study on more patients, and need longer follow-up.

Adolescent

Chromosome and bcr rearrangement in chronic myelogenous leukaemia and their correlation with clinical states and prognosis of the disease.

Among 77 unselected patients with chronic myelogenous leukaemia (CML), 70 had Philadelphia chromosome (Ph1) in blood cells. Extra chromosomal abnormalities were noted in 4%, 55% and 78% of Ph1-positive patients in chronic phase, accelerated phase and acute blast crisis, respectively. Rearrangement of the bcr was detected in 46 of 47 Ph1-positive patients studied and also in three of five Ph1-negative ones. The locations of the breakpoints were mapped to one of four zones of the bcr in 45 patients. The median duration from diagnosis of CML to onset of acute blast crisis was not significantly different between the two groups of patients with breakpoints in the 5' portion (34 months), and in the 3' portion (39 months) of the bcr. In addition, the locations of the breakpoints within the bcr did not change as the disease progressed in the six patients who had DNA analysed both in the chronic phase and subsequently in transformation. In one of them, an additional aberrant band which was not present in the beginning of the acute phase was detected in blood cells taken 2 months later. It is suggested from the studies that transformation of CML may not be related to alterations within the bcr.

Adolescent

Cytogenetic evidence of multifocal origin of a unilateral retinoblastoma. A help in genetic counseling.

Retinoblastoma (Rb) occurs in two different genetic forms, hereditary and nonhereditary. Patients with nonhereditary Rb have unilateral, unifocal tumors, and those with the hereditary form usually have bilateral, multiple tumors. However, about 15% of patients with unilateral disease actually have multifocal tumors due to the hereditary form of Rb. Distinction between unilateral hereditary and sporadic Rb is very important both to the patient, who is at risk of later development of other malignancies, and to any future siblings and offspring. With only clinical data, the discrimination may be difficult. The cytogenetic detection of multiple unrelated clones in the tumor is very helpful for differential diagnosis because this finding strongly suggests the presence of a prezygotic germ cell mutation, which is heritable. A 23-month-old Chinese boy was found to have a single retinoblastoma at the right eye. Cytogenetic study of the tumor cells revealed three abnormal clones. Two of them were related, but the third one had completely different markers, suggesting a hereditary, multifocal origin of the tumor. None of the three clones showed an abnormality of 13q, which is present in about 21% of all Rb patients.

Chromosome Banding