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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Moloney Murine Leukemia Virus (MoMuLV) causes T cell neoplasms in rodents but is not known to be a pathogen in primates. The core protein and enzyme genes of the MoMuLV genome together with an amphotropic envelope gene are utilized to engineer the cell lines that generate retroviral vectors for use in current human gene therapy applications. We developed a producer clone that generates a very high concentration of retroviral vector particles to optimize conditions for gene insertion into pluripotent hematopoietic stem cells. This producer cell line also generates a much lower concentration of replication-competent virus that arose through recombination. Stem cells from rhesus monkeys were purified by immunoselection with an anti-CD34 antibody, incubated in vitro for 80-86 h in the presence of retroviral vector particles with accompanying replication-competent virus and used to reconstitute recipients whose bone marrow had been ablated by total body irradiation. The retroviral vector genome was detected in circulating cells of five of eight transplant recipients of CD34+ cells and in the circulating cells of two recipients of infected, unfractionated bone marrow mononuclear cells. Three recipients of CD34+ cells had a productive infection with replication-competent virus. Six or seven mo after transplantation, each of these animals developed a rapidly progressive T cell neoplasm involving the thymus, lymph nodes, liver, spleen, and bone marrow. Lymphoma cells contained 10-50 copies of the replication-competent virus, but lacked the retroviral vector genome. We conclude that replication-competent viruses arising from producer cells making retroviral vectors can be pathogenic in primates, which underscores the importance of carefully screening retroviral producer clones used in human trials to exclude contamination with replication-competent virus.
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PMID:Helper virus induced T cell lymphoma in nonhuman primates after retroviral mediated gene transfer. 138 75

We studied gene rearrangement and expression of immunoglobulin heavy (IgH) chain, T cell receptor (TCR) beta, gamma and delta chains in neoplastic T cells from patients with leukemia and lymphoma. Rearrangements of TCR beta and gamma chain genes were observed in most of T cell neoplasms. TCR delta chain gene rearrangements or deletions were detected in all 77 T cell neoplasms; 6 of 9 CD3- T cell neoplasms showed rearrangement, whereas biallelic deletion of TCR delta chain gene was the most common pattern in CD3+ T cell neoplasm (65 of 68 patients). One patient with CD3- T cell leukemia had TCR delta chain gene rearrangement with a germline configuration of TCR beta, gamma and IgH chain genes. TCR gamma and delta chain gene transcripts were detected in most of the CD3- T cell neoplasms, whereas mature TCR alpha and beta chain mRNA were demonstrated in the majority of the CD3+ T cell neoplasms. In 6 patients with CD7+ CD3- CD4- CD8- MPO- leukemia, only 2 patients had rearrangements and weak expressions of IgH, TCR gamma and delta chain genes. We also present two cases of double negative (CD3+ CD4- CD8-) leukemia; one is TCR gamma delta bearing LGL, the other is TCR alpha beta bearing ATL. These results suggest that most of T cell neoplasms preserve a pattern of genotypic and phenotypic expression reflecting their developmental pathways and differentiation levels of TCR bearing normal T cells.
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PMID:[Analyses of T cell receptor and its clinical implications in T cell neoplasms]. 189 Jul 39

Using a probe for the newly described bcl-3 gene near the breakpoint of the t(14;19), 176 cases of non-Hodgkin lymphoma and B cell chronic lymphocytic leukemia were analyzed. Rearrangement of the bcl-3 gene was found in only one case; a follicular lymphoma involving the salivary gland that had progressed to a diffuse large cell lymphoma. We conclude that rearrangement of the bcl-3 gene as detected by our method occurs rarely in mature B or T cell neoplasms.
Leukemia 1990 Dec
PMID:Chromosomal translocation t(14;19) as indicated by bcl-3 rearrangement is a rare phenomenon in non-Hodgkin's lymphoma and chronic lymphocytic leukemia: a molecular genetic analysis of 176 cases. 224 4

The rearranging antigen receptor genes of lymphoid cells serve as unique clonal markers of lymphoid neoplasms. Gene rearrangement analysis is a highly sensitive and reproducible tool which is useful in the diagnosis and classification of malignant lymphoma/leukemia. Although clonality can often be determined among B cell neoplasms by virtue of immunoglobulin isotype analysis, no such phenotypic marker of clonality exists for T cells. Therefore, clonality of T lymphoproliferative processes is most readily determined by rearrangement analysis of the T cell antigen receptor genes. The alpha, beta, gamma, and delta genes of the T cell receptor gene family encode heterodimeric surface antigen receptors and undergo rearrangement early in T cell differentiation. Identification of rearrangement of T cell antigen receptor genes provides valuable diagnostic information concerning cellular lineage, clonality and classification of T cell neoplasms. This molecular approach is applicable to the diagnosis of occult disease, relapse, and resolution of diagnostic dilemmas in any type of tissue sample including fluids and needle aspirations.
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PMID:T-cell receptor gene rearrangements and the diagnosis of human T-cell neoplasms. 225 88

We analyzed the rearrangement of TcR delta chain gene in 179 cases of hematological malignancies. In 17 T-cell lines, RPMI 8402, DND41, Peer, and Molt 13 had delta rearranged band (s). Except for RPMI 8402, these cell lines expressed functional delta gene. All of those gamma delta-T-cell lines had short message (1 kb) of TcR beta gene. These findings suggest differences between alpha beta-T-cells and gamma delta-T-cells. All 9 cases of T-ALL/LBL, of which 4 had neither gamma nor beta gene rearrangement, had a new rearranged band of TcR delta locus. This rearrangement was observed in 63% of B-lineage ALL/LBL. In the other T-lymphoproliferative disorders, only 2 cases of AILD and 1 of T-cell lymphoma had the rearranged band (s), showing derived T-cell neoplasm from gamma delta-T-cell as minority. In B-leukemia/lymphoma and myelocytic leukemia, 15% of the cases had the delta rearrangement. Heterogenous findings of TcR delta locus analysis were observed in ATLL without proviral HTLV-I DNA, T-cell lymphoma, AILD and HD. The J delta 1 region was frequently used and the J delta 2 region was rearranged in one AILD. It is suspected that J delta 3 was used in one T-ALL/LBL. There was no correlation between the phenotypic pattern of CD3, CD4, and CD8 in T cell disorders and the rearrangement of the TcR delta gene. These findings suggest that the newly identified TcR delta chain gene rearranges at a very early stage of T cell ontogeny; prior to the other TcR genes and perhaps at almost the same differentiation level as that of CD7 expression. The TcR delta gene is useful in evaluating clonality for the most immature T cell neoplasms not showing rearrangement of the other TcR genes. This gene is not lineage specific, however, when used in conjunction with IgHC gene, it may be a useful tool for the study of ALL/LBL.
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PMID:Analysis of T-cell receptor delta chain gene in hematological malignancies. 253 58

This study demonstrates that the detection of rearrangement of the T-cell receptor gene and adult T cell leukemia virus or human T cell lymphotropic virus type I (ATLV/HTLV-I) integration in the genome are sensitive and practical methods for the diagnosis and characterization of cutaneous T cell neoplasms. Biopsy specimens obtained from small skin nodules containing a dense infiltration of lymphocytes were analyzed by Southern blotting with the use of probes for both the beta-chain of the T-cell receptor gene and the ATLV/HTLV-I genome. DNA samples from one patient with early, chronic adult T cell lymphoma or leukemia, revealed the monoclonal proliferation of lymphocytes. For another patient with early cutaneous T cell lymphoma analysis by Southern blotting with the beta-chain probe of DNA from three separate lesions revealed identical rearranged bands, indicating not only the monoclonal proliferation of T cells in each lesion but also the clonal origin of each lesion. In contrast, analysis by Southern blotting of DNA samples extracted from three nodules from a patient with lymphomatoid papulosis showed no rearranged band and therefore no clonal proliferation. DNA extracted from blood lymphocytes of these patients failed to hybridize with the probes described above as a rearranged band. These results indicate that analysis of DNA extracted from skin lesions may have diagnostic value in determining monoclonal proliferation of lymphocytes in patients with early stage cutaneous lymphomas.
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PMID:Demonstration of clonal proliferation of T lymphocytes in early neoplastic disease. Studies with probes for the beta-chain of the T cell receptor and human T cell lymphotropic virus type I. 278 63

Rearrangements of T cell receptor beta and gamma chain (T beta and T gamma) genes were analyzed by Southern blot method in samples from 30 patients with adult T cell leukemia (ATL) and 17 patients with non-ATL T cell neoplasms. The DNA probes used were the constant and joining region of T beta gene and the joining region of T gamma gene. Rearranged bands of T beta gene on one or both allelic chromosomes were detected in all neoplastic T cells, even those of smoldering ATL, in which only a small percentage of peripheral blood T cells were detected as leukemic. T gamma gene was rearranged in the cells of all but one patient, the exception being one ATL patient. In order to test whether any given variable region (V) of T beta gene was expressed in ATL cells, two functionally rearranged V beta sequences of ATL were compared with a V beta sequence from T cells acute lymphoblastic leukemia cells. No significant homologies were noted among the three deduced gene product amino acid sequences, confirming that T beta molecules of ATL cells contained no specific structures in common. The observed heterogeneity of T beta and T gamma gene rearrangements in ATL cells further supported these findings.
Leukemia 1988 Feb
PMID:Gene rearrangements of T cell receptor beta and gamma chains in HTLV-I infected primary neoplastic T cells. 289 62

Rearrangements of the T cell gamma (T gamma) gene were studied in primary neoplastic cells from 75 patients with leukemia or lymphoma. T gamma gene rearrangements were observed in 19 of 21 T cell neoplasms; 14 of 21 immature B cell leukemias, including 4 out of 5 patients with rearrangements of both immunoglobulin heavy-chain (JH) and T cell receptor beta chain (T beta) genes; none out of 16 nonlymphoid leukemias. Thus, T gamma gene rearrangement is frequently found in immature B cells and is not always found in T cells showing T beta gene rearrangement, but it is not detected in nonlymphoid cells. Furthermore, T gamma gene rearrangement in cells with the germline configuration of the JH and T beta genes was observed. These results indicate that the detection of T gamma gene rearrangement does not allow a clear assignment to a particular lineage. However, an analysis of T gamma gene rearrangement provides a further potential tool to establish the lymphoid cellular origin and clonality of hematologic neoplasms and identify the normal stages of lymphocyte differentiation.
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PMID:T cell gamma gene rearrangements in hematologic neoplasms. 294 86

The frequency and pattern of T gamma gene rearrangement and expression was investigated in hematopoietic neoplasms including T and B lymphoid and myeloid malignancies. 39 of 39 T lymphoid neoplasms, including fresh cases and cell lines, were found to display clonal T gamma gene rearrangements. There was heterogeneity with respect to utilization of the two T gamma constant region genes, T gamma C1 and T gamma C2. In 31 cases (80%) T gamma C1 was deleted and T gamma C2 was rearranged, while in the remaining 8 cases (20%) T gamma C1 was rearranged. T gamma gene rearrangements were found in non-T cells, but were restricted to 6/17 (35%) immature B cell neoplasms. All 24 mature B cell and 14 myeloid neoplasms retained the T gamma germ line pattern. T gamma mRNA was found in all T cells tested. However, the majority (16/17) of T cells most likely do not express a T gamma protein since a T alpha/beta heterodimer detected by reactivity with the MoAb WT31 is present on the cell surface together with T3. These data suggest that T gamma gene rearrangements are universal in T cells and frequent in immature B cell neoplastic populations. However, expression of the T gamma protein is extremely infrequent, indicating that T cell neoplasms are very rarely derived from the recently identified T3+T gamma +T alpha/beta- peripheral T cell population.
Leukemia 1988 Jan
PMID:Patterns of T cell receptor gamma gene rearrangement and expression in B and T lymphoid malignancies. 312 7

We report the incidence of the chronic lymphoproliferative disorders evolving with leukaemia in Hong Kong. Our findings demonstrate that B cell malignancies are significantly more frequent than mature T cell neoplasms, a picture similar to that seen in Western countries but different from other Eastern countries, eg Japan, where T cell malignancies are more frequent. In contrast to the West, where chronic lymphocytic leukaemia (CLL) is the most common disorder, in Hong Kong there is a clear predominance of B cell lymphomas in leukaemic phase accounting for two-thirds of the cases and particularly those displaying lymphoplasmacytic features or with villous lymphocytes. CLL in Hong Kong has similar clinical and laboratory features to the disease in patients from the West. Distinct disease categories, rare in the West such as the variant form of hairy cell leukaemia and T cell prolymphocytic leukaemia, are also documented. It is unclear whether the differences in prevalence of disease subtypes between Hong Kong and the West relate to different genetic background or environmental factors determinant of the development or progression of the leukaemia. Further studies investigating the genetic/molecular lesions may help to clarify whether the aetiopathogenesis of the lymphoid disorders in Hong Kong is similar to that of Western countries.
Leukemia 1997 Nov
PMID:The spectrum of chronic lymphoproliferative disorders in Hong Kong. A prospective study. 936 33


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