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Biomedical subjects

J Hara

Publications and source records attributed to J Hara.

At least 127 records · Page 7Linked to original sources
PubMed1989

Clonal T-cell lymphoproliferation containing Epstein-Barr (EB) virus DNA in a patient with chronic active EB virus infection.

A 10-year-old boy with chronic active Epstein-Barr virus (EBV) infection developed T-cell lymphoproliferation in the terminal stage of hepatic failure. The phenotypes of the proliferating lymphocytes were CD3+, CD4+ and HLA-DR+. The genomic DNAs from these cells demonstrated two rearranged T-cell receptor beta-chain genes and contained the EBV genome. These findings indicate that EBV can infect T lymphocytes and might cause clonal T-cell lymphoproliferation.

Blotting, Southern↗
PubMed1989

Rearrangement of variable region T cell receptor gamma genes in acute lymphoblastic leukemia. V gamma gene usage differs in mature and immature T cells.

Using probes recognizing variable regions (V gamma) and joining regions (J gamma) of the T cell receptor (TCR) gamma gene, we have analyzed the usage of V gamma genes in 24 patients with T cell acute lymphoblastic leukemia (ALL) and 36 patients with B-precursor ALL. In CD3- T-ALL derived from immature T cells, V gamma genes more proximal to J gamma were frequently rearranged; V gamma 8, V gamma 9, V gamma 10, and V gamma 11 were used in 19 of 24 rearrangements. In contrast, CD3+ T-ALL derived from a more mature stage of T cell ontogeny, showed a high frequency of rearrangements involving V gamma genes distal to J gamma; V gamma 2, V gamma 3, V gamma 4, and V gamma 5 were used in 17 of 25 rearrangements. In B-precursor ALL, no notable bias of V gamma gene usage was observed. This probably reflects the possibility that TCR genes may not rearrange according to a T cell hierarchy when under control of a B cell gene program. Furthermore, deletions of those V gamma genes located 3' to rearranged V gamma genes were observed in all patients analyzed. This supports the theory that loop deletion is a major mechanism for TCR-gamma gene rearrangement.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

CD3-negative lymphoproliferative disease of granular lymphocytes containing Epstein-Barr viral DNA.

Lymphoproliferative disease of granular lymphocytes (LDGL) is a heterogeneous disorder and the pathogenesis is likely to be complex. Some patients with chronic active EBV (CAEBV) infection also have LDGL. To investigate the relationship between EBV infection and the pathogenesis of LDGL, we conducted a survey for EBV DNA sequences by Southern blot analysis of DNA obtained from the peripheral blood of seven patients with LDGL, including one with CAEBV infection. Interestingly, EBV DNA was detected in the sample from the patient with CAEBV infection, and in the samples from four other patients with CD3-LDGL. Moreover, a single band for the joined termini of the EBV genome was demonstrated in two samples, suggesting a clonal disorder of those LDGL. These findings strongly suggest that EBV may play a pathogenic role in some cases of LDGL.

Adolescent↗
PubMed1989

Relationship between rearrangement and transcription of the T-cell receptor alpha, beta, and gamma genes in B-precursor acute lymphoblastic leukemia.

Transcription of the T-cell receptor (TCR)-gamma, beta, and alpha genes has been analyzed in 29 patients with B-precursor acute lymphoblastic leukemia (ALL) by northern blotting analysis. In addition, the configuration of the TCR-alpha gene was examined using newly developed genomic J alpha probes capable of detecting TCR-alpha gene rearrangements involving joining (J)alpha regions up to 85 kilobase (kb) from constant (C)alpha. In this study, TCR-alpha gene rearrangements were detected in 16 of the 29 patients. Thus, the frequency of TCR-alpha gene rearrangements in B precursor ALL was as high as with TCR-gamma (15 of 29) and was higher than observed for TCR-beta (nine of 29). Truncated transcripts were frequently observed in cells with rearrangements of the TCR-beta or alpha gene. In contrast, TCR-gamma transcripts were detected in only one patient despite the high incidence of TCR-gamma gene rearrangements. Results presented here suggest that although expression of TCR genes was weak in B-precursor ALL cells compared with T-lineage cells, these genes experience both transcriptional and recombinational crossover in B-precursor ALL. The results also suggest that neither transcription nor gene rearrangement, when examined alone, are sufficient to assign T or B lymphocyte lineage in lymphoblastic leukemia.

Adolescent↗
PubMed1989

The molecular analyses of hematological malignancies--lineage specific classification and its clinical implications.

Cells from 203 children with leukemia/lymphoma were analyzed by the FAB (French-American-British) system using a broad panel of markers such as immunological marker studies, Southern blot and Northern blot analyses to establish a lineage specific classification of childhood leukemia. Phenotypically, they were divided into B-lineage (62.6%), T-lineage (9.8%), non-lymphoid (14.3%) and uncertain lineage (13.3%). Two B-lineage ALL cells and two T-lineage ALL cells studied did not show immunoglobulin (Ig) or T-cell receptor (TCR) gene rearrangements, respectively. Therefore, those four cases were excluded from the final classification. The uncertain lineage leukemia, which includes undifferentiated leukemia and mixed lineage leukemia, were further subclassified at the DNA and RNA levels. The definitions of B-lineage and T-lineage cells, incidence of dual genotypes or spillover, heterogeneity of undifferentiated leukemia, and a new classification for mixed lineage leukemia were discussed.

Child↗
PubMed1989

Molecular analysis of acute undifferentiated leukemia: two distinct subgroups at the DNA and RNA levels.

On the basis of negativity for myeloperoxidase (MPO) and absence of lineage-associated antigens on the cell surface, 11 children were diagnosed as having acute undifferentiated leukemia. To analyze the molecular events associated with hematopoietic cell differentiation, we analyzed the configuration of the immunoglobulin (Ig) and T-cell receptor (TCR) delta, alpha, gamma, and beta genes in these patients. In parallel, transcription of the genes for MPO, terminal deoxynucleotidyltransferase (TdT), CD3-gamma, Ig-mu, TCR-gamma, and beta was also examined. Six patients showed rearrangements of both the Ig heavy (H) and TCR-delta genes, frequently accompanied with Ig-kappa, TCR-alpha, gamma, and beta gene rearrangements. These findings indicated that the leukemic cells from the six patients had been committed to the lymphoid lineage. This concept was supported by the presence of TdT transcripts in three analyzed specimens from these patients. In contrast, the remaining five patients did not display rearrangements of the Ig or TCR genes, and TdT transcripts were undetectable in two patients tested. MPO transcripts were not detected in four patients analyzed, thus providing no evidence of myeloid differentiation. After hybridization with the CD3-gamma gene, three of six patients showed transcription of the CD3-gamma gene. In addition to CD3-gamma transcripts, one patient with rearrangements of the Ig-H, TCR-delta, alpha, gamma, and beta genes also had full-length TCR-beta and gamma transcripts, indicating a T-precursor-cell origin of the leukemic cells from this patient. The Ig and TCR genes were in the germline configuration in the other two patients with CD3-gamma transcripts. One of them did not express the CD7 antigen but did express the CD33 antigen on the cell surface, suggesting that CD3-gamma transcription may not always be an event restricted to cells differentiating along the T-cell lineage.

Acute Disease↗
PubMed1988

Comparison of T cell receptor alpha, beta, and gamma gene rearrangement and expression in T cell acute lymphoblastic leukemia.

We have analyzed the configuration of the T cell receptor (TCR) alpha gene using newly developed genomic joining region (J alpha) probes, which cover approximately 80 kb of the J alpha region upstream from the constant region in 19 patients with T cell acute lymphoblastic leukemia (T-ALL) and in three CD3- leukemic T cell lines (HSB2, CEM, and MOLT4). In parallel, transcription of the TCR-alpha, beta, and gamma genes was examined in 11 of these patients and in the T cell lines. All T-ALL and the three T cell lines exhibited both TCR-gamma and beta gene rearrangements. 8 of 10 T-ALL and all T cell lines expressed TCR-gamma transcripts. All samples tested expressed both TCR-beta and CD3-gamma transcripts. TCR alpha transcripts were only observed in CD3+ T-ALL but not in CD3- T-ALL or the CD3- cell lines. Among the CD3+ T-ALL, eight had TCR-alpha gene rearrangements. In addition, TCR-alpha gene rearrangements were detected in one CD3- T-ALL and all three T cell lines. These leukemic cells may represent a transient stage between rearrangement and expression and provide an opportunity for analyzing the mechanism regulating the expression of the TCR-alpha gene.

DNA, Neoplasm↗
PubMed1988

T cell receptor delta gene rearrangements in acute lymphoblastic leukemia.

Using a newly isolated cDNA clone encoding the TCR-delta gene and genomic probes, we have analyzed T cell receptor (TCR) delta gene rearrangement in 19 patients with T cell acute lymphoblastic leukemia (T-ALL) and 29 patients with B-precursor ALL. Five out of seven CD3- T-ALL and 4 of 12 CD3+ T-ALL showed bi-allelic rearrangements of the TCR-delta gene. In three CD3+ patients, a single allelic TCR-delta gene rearrangement was observed with rearrangement of the TCR-alpha gene on the other allele. In five CD3+ patients with bi-allelic rearrangements of the TCR-alpha gene, the TCR-delta gene locus was deleted. Transcription of the TCR-delta gene was also analyzed in six T-ALL. Five patients expressed TCR-delta transcripts. Only one T-ALL, presumably derived from the most immature T lineage cells, did not have TCR-delta transcripts, but expressed TCR-gamma and 1.0-kb truncated TCR-beta transcripts. In B-precursor ALL, 20 patients (69%) showed rearrangements of the TCR-delta gene. The frequency of TCR-delta gene rearrangement was higher than TCR-alpha (59%), gamma (52%), or beta (31%) genes. These findings suggest that TCR-alpha gene rearrangements may take place after rearrangements of the TCR-delta gene with concomitant deletion of rearranged TCR-delta genes in T cell differentiation. Among leukemic cells of B lineage, the TCR-delta gene is the earliest rearranging TCR gene, followed by TCR-gamma and beta gene rearrangements.

Blotting, Southern↗
PubMed1987

Concomitant rearrangements of T-cell beta- and gamma-chain genes in childhood T-lineage leukemia/lymphoma.

Similar to the immunoglobulin (Ig) gene rearrangements in B-lineage cells, identification of T-cell receptor (TCR) gene rearrangements is a novel clonal marker and necessary to establish a T-cell lineage. The function of T-cell gamma-chain (T gamma) gene is still unknown, but because of its shared properties with T-cell alpha-chain (T alpha) and T beta genes, we analysed T gamma gene organization in 10 patients with T-lineage leukemia/lymphoma as well as in non-T lineage leukemias. All 10 cases of T-lineage leukemia/lymphoma, whose phenotypes were different, demonstrated T gamma gene rearrangements as well as T beta gene rearrangements. In contrast, among the non-T-lineage leukemias, the emergence of T beta and/or T gamma gene rearrangements was varied. Based on these findings, concomitant rearrangements of T beta and T gamma genes are characteristic in childhood T-lineage leukemia/lymphoma regardless of their phenotypic differences. Furthermore, no obvious developmental hierarchy was observed between T beta and T gamma gene arrangements in these leukemia/lymphoma cells.

Antibody Diversity↗
PubMed1987

T cell receptor alpha-chain gene rearrangements in B-precursor leukemia are in contrast to the findings in T cell acute lymphoblastic leukemia. Comparative study of T cell receptor gene rearrangement in childhood leukemia.

We have analyzed T cell receptor alpha-chain gene configuration using three genomic joining (J) region probes in 64 children with acute lymphoblastic leukemia (ALL). 11 out of 18 T-ALLs were T3 positive; alpha-chain gene rearrangements were demonstrated in only two of 18, indicating that the majority of T-ALLs would have rearrangements involving J alpha segments located upstream of these probes. In contrast, 15 out of 46 B-precursor ALLs showed rearrangements of the alpha-chain gene and J alpha segments located approximately 20-30 kb upstream of the constant region were involved in 13 of these patients. Nine of 15 B-precursor ALLs with rearranged alpha-chain genes had rearrangements of both gamma- and beta-chain genes, whereas the remaining six had no rearrangements of gamma- and beta-chain genes. These findings indicated that alpha-chain gene rearrangement is not specific for T lineage cells and gamma- and/or beta-chain gene rearrangement does not appear essential for alpha-chain gene rearrangement, at least in B-precursor leukemic cells.

B-Lymphocytes↗
PubMed1987

Rearrangement of the T cell receptor gamma-chain gene in childhood acute lymphoblastic leukemia.

We analyzed rearrangements of the T cell receptor gamma-chain (T gamma) gene as well as rearrangements of the T cell receptor beta-chain (T beta) gene and immunoglobulin heavy-chain (IgH) gene in 68 children with acute lymphoblastic leukemia (ALL). All 15 patients with T cell ALL showed rearrangements of both T beta and T gamma genes. Twenty-four of 53 non-T, non-B ALL patients (45%) showed T gamma gene rearrangements and only 14 of these also showed T beta gene rearrangements. Only a single patient rearranged the T beta gene in the absence of T gamma gene rearrangement. The rearrangement patterns of the T gamma gene in non-T, non-B ALL were quite different from those observed in T cell ALL, as 20 of 23 patients retained at least one germline band of the T gamma gene. In contrast, all T cell ALL patients showed no retention of germline bands. These data indicate that rearrangement of the T gamma gene is not specific for T cell ALL. Further, the results also suggest that T gamma gene rearrangement precedes T beta gene rearrangement. The combined analysis of rearrangement patterns of IgH, T beta, and T gamma genes provides new criteria for defining the cellular origin of leukemic cells and for further delineation of leukemia cell heterogeneity.

Antigens, Neoplasm↗
PubMed1987

Heterogeneity of acute undifferentiated leukemia at the immunoglobulin and T-cell receptor genes level.

Phenotypic markers of leukemic cells from 76 children with acute leukemia were examined. Of these cases, 7 were diagnosed as acute undifferentiated leukemia (AUL) whose leukemic cells were negative for myeloperoxidase and did not react with lineage-specific or lineage-associated monoclonal antibodies. Then, we analyzed the configuration of both immunoglobulin (Ig) and T-cell receptor beta-chain (T beta) gene in these 7 AUL cases. Three cases had no rearrangement of Ig or T beta genes which was suggestive of non-lymphoid origin of these cases. In contrast, 4 cases showed rearrangements of Ig and/or T beta genes. One of these 4 cases demonstrated T beta gene rearrangement with retention of the germline configuration of Ig genes. Two cases with both Ig and T beta gene rearrangements also showed kappa-chain gene rearrangements. These findings indicate the heterogeneity of AUL at the DNA level, and may cast new light on the early differentiation of hematopoietic progenitor cells.

Acute Disease↗
PubMed1986

Kappa-chain gene rearrangement in an apparent T-lineage lymphoma.

We describe a 10-yr-old boy with T-lineage non-Hodgkin's lymphoma. He had a mediastinal mass, swollen supraclavicular lymph nodes, and pleural effusion. A supraclavicular lymph node biopsy under light microscopy showed a malignant lymphoma of diffuse lymphoblastic type. Most of the cells taken from the malignant pleural effusion expressed T cell-associated antigens such as Leu-1 and OKT 8. To confirm these antigens as T-lineage lymphoma, we examined genomic DNA from malignant cells obtained from the pleural effusion. As was expected, T cell receptor beta-chain gene rearrangements were demonstrated. However, when the immunoglobulin gene organization was analyzed, we detected rearrangements in both the heavy- and kappa-chain genes. To our knowledge, this is the first case in which kappa-chain gene rearrangement was detected in apparent T-lineage cells. These findings provide important information relating to determination of the cellular lineage of lymphoid malignancy.

Child↗
PubMed1986

Further heterogeneity of childhood common acute lymphoblastic leukemia.

In an attempt to look further at the problem of heterogeneity, we have studied the immunoglobulin (Ig) gene organization in leukemic cells from 20 children with acute lymphoblastic leukemia (common ALL). Nineteen cases were divided into two subgroups: 12 cases with rearrangement of the Ig heavy (H) chain genes and 7 cases with rearrangement of both the Ig H and light (L) chain genes. No Ig gene rearrangement was found in one case. These findings indicate that there is more heterogeneity among patients with common ALL than has previously been believed.

Antigens, Neoplasm↗