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.
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.
Nine children with mediastinal non-Hodgkin's lymphoma (NHL) were treated according to our new regimen which is characterized by intensified therapy with highdose cytosine arabmoside (HDCA). After induction therapy with a combination of five drugs, such as vincristine, doxorubicin, cyclophosphamide, l-asparaginase, and prednisolone, intermediate dosages of methotrexate (MTX) (1 g/m2) and HDCA (1.5 g/m2 X 12 doses) were administered. All but one patient (88.9%) achieved complete remission and then received this intensified therapy. With a median follow-up period of 25.5 months, five patients are still in complete remission, but three patients have relapsed. From the phenotypic point of view, these relapsed patients showed only very immature T-cell differentiation antigens such as 0 2 and CD7 (or CD5). These results suggest that HDCA as intensified therapy for children with mediastinal NHL seems to be effective. However, for patients with an immature phenotype of T-lineage cells, more sophisticated regimens should be prepared.
T cell-depleted C3H/He or (C57BL/6xC3H/He)F1 (B6C3F1) mice were prepared by adult thymectomy and injection of antithymocyte serum, followed 3 wk later by lethal x-irradiation and bone marrow reconstitution. When these T cell-depleted mice were not injected or injected i.v. with normal spleen and lymph node cells treated with either anti-Thy-1, -L3T4 or -Lyt-2 antibody plus C or C alone, none of the groups of mice developed thyroiditis. In contrast, the adoptive transfer of normal cells treated with anti-Lyt-1 plus C resulted in high incidence of the production of antithyroglobulin antibody and the induction of typical thyroiditis lesion. The thyroid was the sole organ involved, because neither typical inflammatory lesion in other organs nor autoantibody such as anti-DNA antibody was detected in mice that exhibited thyroiditis. Analyses of surface phenotypes of cells required for inducing thyroiditis by the adoptive transfer revealed that an appreciable percentage of Lyt-1 dull T cells remained after the treatment of normal lymphoid cells with anti-Lyt-1 plus C. Almost all of these Lyt-1 dull T cells expressed magnitudes of L3T4 or Lyt-2 Ag comparable to those detected on Lyt-1 bright T cells. More important, the induction of thyroiditis was almost completely prevented by either in vitro or in vivo elimination of Lyt-1 dull L3T4+(bright) but not of Lyt-1 dull Lyt-2+(bright) T cells. These results indicate that Lyt-1 dull L3T4+ T cells existing in normal healthy individuals have potential to induce typical thyroiditis which is associated with the production of antithyroglobulin autoantibody, and that the activation and/or function of this T cell subset is regulated by the Lyt-1 bright T cell population coexisting in normal lymphoid cell population.
The T‐cell receptor β‐chain (Tβ) gene expression was examined in 16 children with B‐lineage acute lymphoblastic leukemia (ALL), including eight patients with rearrangement of the Tβ gene as well as immunoglobulin (Ig) heavy chain gene rearrangement. In contrast to the 1.3 kb full‐length transcripts of the Tβ gene observed in T‐lineage leukemia and lymphoma cells, no transcript of the Tβ gene was detected in 10 patients, including four with Tβ gene rearrangement. Low levels of Tβ transcripts were found in three patients with Tβ gene rearrangement and two patients without Tβ gene rearrangement, but those transcripts were truncated. In contrast to those findings, a single patient with Tβ gene rearrangement showed abundant 1.3 kb Tβ transcripts. These data indicate that Tβ gene expression is not restricted to T‐lineage cells and demonstrate the heterogeneity of B‐lineage ALL at the expression level of the Tβ gene. Our findings also suggest that Tβ gene expression is not always accompanied with Tβ gene rearrangement.
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