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M Minden

Publications and source records attributed to M Minden.

53 records · Page 3Linked to original sources
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↗
PubMed1988

Rearrangement of T-cell delta locus in lymphoproliferative disorders.

Studies of lymphoproliferative disorders using immunoglobulin and T-cell receptor genes have contributed to our understanding of clonality and lineages of these disorders. In this study, we examined the rearrangement of the recently discovered T-cell delta chain genes in a variety of lymphoproliferative diseases. We show here that six of 14 T-cell lymphomas and five of 23 B-cell lymphomas or B-cell leukemia cell lines have rearranged the delta loci, while two of two hyperimmune reactions retain germline configuration within these genes. Seven of ten cases of AILD were rearranged, and Lennert's lymphoma, which has been previously described as a T-cell malignancy, also contains rearrangements in the delta chain genes (three of five). Large cell anaplastic lymphomas positive for the activation antigen CD 30 also contain rearrangement in about one-half (five of 11) of the tumors examined. Two of seven of the Hodgkin's lymphomas studied contained a rearrangement for this gene. This study indicates that this newly identified T-cell delta gene is useful in evaluating clonality but is not lineage specific. However, with only one exception (in 28 rearrangements), this gene rearranges in tumors with gamma and beta chain gene rearrangements, indicating that when used in conjunction with the other TcR genes, delta rearrangement may also be useful in evaluating lineages.

B-Lymphocytes↗
PubMed1987

Idiopathic small airways pathology in patients with graft-versus-host disease following allogeneic bone marrow transplantation.

In a retrospective analysis (July 1979 to March 1984) of 120 allogeneic adult bone marrow transplant recipients, we identified seven patients with small-airway disease for whom no microbiologic agent was detected. Six had pulmonary function studies demonstrating air flow obstruction. Five of the seven patients had an open-lung biopsy showing pathologic changes within small airways; these varied from early bronchiolar wall damage to bronchiolitis obliterans. The inflammatory cell infiltrate was peribronchiolar, and consisted of polymorphonuclear leukocytes and lymphocytes in varying proportions. Three of the seven patients recovered following increased immunosuppressive therapy; the other four died. Because all seven patients had acute and chronic graft-versus-host disease, in the absence of any identifiable pathogen, we postulate that small-airway damage represents one of the facets of graft-versus host-disease. An additional analysis of 26 patients with respiratory symptomatology and available histologic material supports the hypothesis that small-airway disease in bone marrow transplant patients represents a risk factor for the subsequent development of respiratory opportunistic infections.

Bone Marrow Transplantation↗
PubMed1986

Rearrangement and expression of the alpha, beta, and gamma chain T cell receptor genes in human thymic leukemia cells and functional T cells.

Using cDNA and genomic probes representing the alpha, beta, and gamma chain of the human T cell receptor genes, we have examined the structure and expression of these genes in 14 human leukemic T cell lines, representing different stages of thymic differentiation, and 15 functional human T cell clones. Rearrangement of the gamma and beta chain genes was found in all of the functional T cell clones and all but one (P30/OKUBO) thymic leukemia cell line; all of the lines that had rearrangement of the beta chain expressed beta mRNA. Expression of the alpha chain was found in all of the functional T cell clones examined, while rearrangement of the alpha chain gene, using currently available probes to the J region, could be shown in 10 of 13 functional clones. In contrast, expression of the alpha chain was found in 6 of 10 leukemic T cell lines, while rearrangement was found in six of these nine cell lines. Of the 14 leukemic cell lines studied for rearrangement of the alpha chain, rearrangement was found in six cases. The data obtained with the cell lines are consistent with an ordered rearrangement and expression of the gamma, beta, and alpha chains of the T cell antigen receptor (TcR) genes. The leukemic cell lines used in the present study have previously been characterized with regard to cell surface antigens and intracellular enzymes. Based on those results a scheme of thymic development was proposed. The developmental stages identified by those studies are not in complete agreement with stages of T cell development, as determined in the present study using molecular probes.

Cell Line↗
PubMed1986

Single allelic C mu gene rearrangements in patients with T cell and undifferentiated leukemia.

By using a panel of monoclonal antibodies in combination with conventional morphological and histochemical studies, seven leukemic patients were diagnosed as having T-cell lymphocytic leukemia (ALL) and three patients were classified as having acute undifferentiated leukemia (AUL). When genomic DNA from each patient was analysed by the Southern blot hybridization technique, two out of seven cases with T-cell ALL and two of three cases with AUL demonstrated immunoglobulin (Ig) mu gene rearrangements. Interestingly, the patterns of C mu gene rearrangement found in these four cases as well as in the T-cell line HSB-2 were quite similar with rearrangement of a single allele and germ line configuration retained in the other allele. Ig gene rearrangement is an essential property of cells of B-lineage, but detection of an Ig gene rearrangement by itself seems insufficient to assign commitment to B-lineage differentiation. The significance of Ig gene rearrangements in T-cell ALL is unclear, but this heterogeneity at the DNA level among T-cell ALL may reflect differences in leukemogeneis and have prognostic and therapeutic implications.

Alleles↗
PubMed1986

Rearrangement of the beta chain of the T cell antigen receptor and immunoglobulin genes in lymphoproliferative disorders.

55 samples representing Hodgkin's and non-Hodgkin's lymphoma and other hyperplastic lesions of the lymph node were examined for rearrangement of the beta chain of the T cell antigen receptor (TcR) and Ig genes. In non-Hodgkin's lymphoma, rearrangement of TcR beta was found in all 14 T cell lymphomas and in two of the seven B cell lymphomas. Ig gene rearrangement was found in none of the 14 T cell lymphomas and in all seven B cell lymphomas. We also examined DNA from lymph nodes in which the lineage of the malignant cell is not clear. Rearrangement of TcR beta was found in all five lymphoepitheloid cell (Lennert's) lymphomas; four of eight Hodgkin's lymphomas; seven of ten Ki 1+ lymphomas; and all nine cases of angioimmunoblastic lymphoadenopathy (AIL). Ig gene rearrangement was found in none of five lymphoepitheloid cell lymphomas; none of eight Hodgkin's lymphomas; three of ten Ki 1+ lymphomas; and four of nine cases of AIL. These findings indicate that genetic studies of TcR and Ig genes are useful in identifying the presence of a clonal population in a lymph node, in determining the extent of the clonal population, and aid in identifying lineage. Of special interest was the finding that some cases of Hodgkin's lymphoma and AIL contain clonal rearrangement of the TcR genes, which suggests that in those cases the malignant cells may be of T cell origin.

DNA↗
PubMed1985

Rearrangement of the T-cell receptor beta-chain gene in non-T-cell, non-B-cell acute lymphoblastic leukemia of childhood.

We studied 50 patients with childhood acute lymphoblastic leukemia (ALL), including 11 with T-cell ALL and 39 with non-T-cell, non-B-cell ALL. In addition to characterizing surface-antigen expression and immunoglobulin-gene rearrangement, we determined whether the T-cell receptor beta-chain gene also undergoes somatic rearrangement. All 11 patients with T-cell ALL had rearrangements of the beta-chain gene, with no persistence of the germline configuration. In two of these patients we demonstrated rearrangements of both the T-cell receptor gene and the immunoglobulin mu-heavy-chain gene. All 39 patients with non-T-cell, non-B-cell ALL had immunoglobulin heavy-chain gene rearrangements; in addition, 10 had rearrangements of the T-cell receptor beta-chain gene, indicating heterogeneity at the level of the T-cell receptor gene in this form of the disease. The results of our analysis of T-cell receptors and immunoglobulin heavy-chain genes offer new insight into normal and abnormal lymphocyte differentiation.

Alleles↗
PubMed1985

Phenotypic heterogeneity at the DNA level in childhood leukemia with a mediastinal mass.

Although phenotypic heterogeneity of childhood T-cell acute lymphocytic leukemia (T-ALL) which bear receptors for sheep red blood cells (E-rosettes) and/or T-cell-associated antigens has been reported, there are certain clinical features which are shared by most patients. A mediastinal mass is one of the most characteristic presentations in this particular disorder. This report describes four children with ALL, who presented with a mediastinal mass. Three patients were E-rosette-negative and one was E-rosette-positive. Individual surface phenotypes, defined by a panel of monoclonal antibodies, were quite different. Since Ig gene organization is an essential property of cells of B-lineage, it was surprising to find that analysis of genomic DNA revealed immunoglobulin (Ig) gene rearrangements in two of them. These findings suggest that there is significant heterogeneity even among those leukemias associated with a mediastinal mass, and that a mediastinal mass may not clearly indicate origin from cells of T-lineage. This heterogeneity may reflect differences in leukemogenesis and may have prognostic and therapeutic implications.

Antibodies, Monoclonal↗
PubMed1985

Analysis of cDNA clones specific for human T cells and the alpha and beta chains of the T-cell receptor heterodimer from a human T-cell line.

We report the isolation and characterization of 19 classes of nonrearranging T cell-specific cDNA clones and two cDNA clones encoding the alpha and beta chains of the T-cell antigen receptor from a human T-cell line, Jurkat. Results indicate that the human alpha-chain gene, like its beta-chain counterpart, undergoes somatic rearrangement in T cells. In addition, it shows sequence homology to its beta-chain counterpart and immunoglobulin, indicating that the human alpha chain is also a member of the immunoglobulin supergene family. Sequence comparison suggests that the alpha chain also may be composed of variable (V), diversity (D), joining (J), and constant (C) region gene segments. The protein deduced from the cDNA sequence has a molecular weight of 29,995 and possesses six potential N-glycosylation sites. The availability of alpha- and beta-chain genes of the T-cell receptor from the same T-cell line provides tools to study their possible roles in recognition of antigens and major histocompatibility complex products by the human T-cell receptor.

Amino Acid Sequence↗
PubMed1985

Analysis of commitment of human leukemia HL-60 cells to terminal granulocytic maturation.

Analysis of commitment of human promyelocytic leukemia HL-60 cells to terminal granulocytic maturation induced by dimethyl sulfoxide (DMSO) or retinoic acid (RA) was accomplished using biochemical measurements and a plasma clot clonal assay system that permits a high plating efficiency of 40 to 60%. Commitment to granulocytic maturation occurs very rapidly. When cells are exposed to these inducers for only 8 to 18 h, an interval much shorter than a single generation time, and are then subcultured in inducer-free plasma clots, they demonstrate a decrease in proliferative capacity and form colonies composed of mature nitroblue tetrazolium (NBT)-positive cells along with occasional colonies containing both NBT-positive and NBT-negative cells; in both types of colony, the NBT-positive cells are widely dispersed. Undifferentiated HL-60 cells give rise to compact NBT-negative colonies of large size without cell migration. HL-60 cell differentiation induced by either DMSO or RA is associated with a progressive decline in both DNA and RNA synthesis; this includes transcriptional inactivation of ribosomal DNA sequences. In contrast to DMSO, which induces development primarily of metamyelocytes, RA treatment leads to the accumulation of more mature band and segmented neutrophils; sequential exposure of cells pretreated with DMSO to RA alone fails to cause rapid appearance of segmented neutrophils. From these studies, we conclude that HL-60 cells become very rapidly committed to terminal maturation and that DMSO and RA appear to induce granulocytic maturation via two different mechanisms.

Cell Differentiation↗
PubMed1984

Immunoglobulin mu-chain gene rearrangement in a patient with T cell acute lymphoblastic leukemia.

A 6-yr-old girl with T cell acute lymphoblastic leukemia (ALL) is described. She had a mediastinal mass and her leukemic cells expressed T cell-associated antigens (Leu 1+, OKT3+, OKT9+, and OKT10+). When we examined genomic DNA from the leukemic cells, we detected Ig mu-chain gene rearrangement with germ-line configuration of light chain genes. As reported recently, detecting Ig gene rearrangement has become an important procedure for further classifying B cell precursor cells. This case, however, suggests that there is also heterogeneity among patients with T cell ALL, not only at the level of cell surface phenotypes, but also at the level of the Ig gene. These findings have major implications when we consider both the ontogenesis of these leukemic cells and the normal differentiation of human lymphocytes.

Antigens, Surface↗
PubMed1984

Immunoglobulin gene rearrangement in acute myelogenous leukemia.

Twenty-one cases of newly diagnosed nonlymphocytic leukemia were subjected to analysis of immunoglobulin gene organization. Although immunoglobulin gene organization is an essential property of B-lineage cells, immunoglobulin gene rearrangement has also been observed in mouse T-cells and occasionally in cultured human T-cell leukemic cells. Here we report the first case of acute myelogenous leukemia in which mu-chain gene rearrangement is demonstrated. This finding provides a further step in our understanding of both normal and abnormal hematopoietic cell differentiation and the heterogeneity of nonlymphocytic leukemia.

Acute Disease↗
PubMed1983

Generation time of leukaemic blast progenitor cells.

Previous studies have indicated that the generation time of human leukaemic cells is longer than that of normal haematopoietic cells. We have employed a modification of the thymidine (TdR)-suicide technique to measure directly the generation time of leukaemic progenitor cells capable of colony formation. The results obtained with two human leukaemic cell lines (KG-1 and HL-60) and with blast progenitor cells from two patients with acute myelogenous leukaemia indicate generation times ranging from 9 X 0-22 X 0 hr and S-phase durations ranging from 5 X 5-8 X 0 hr. Using the same technique, the generation time of normal bone marrow CFU-c was determined to be 9-11 hr. These findings suggest that the proliferation rate of human leukaemic blast progenitor cells is similar to that of normal haematopoietic stem cells.

Adolescent↗
PubMedDate not supplied

Rearrangements of T-cell receptor gene YT35 in human DNA from thymic leukaemia T-cell lines and functional T-cell clones.

An essential property of the immune response is its ability to distinguish between self and non-self and to generate enormous diversity in antibody and T-cell immune responses. Although the genetic and molecular mechanisms responsible for antibody diversity have now largely been elucidated, the structure of the T-cell receptor and the diversification of the receptor repertoire have only recently become amenable to study. One approach has involved immunochemical studies of the protein precipitated by monoclonal antibodies which react specifically with the immunizing T-cell clones. Another approach has been to clone and sequence a human or a murine T-cell specific message that may specify part of the T-cell receptor. We present here results of Southern blot analysis of non-T, immature T, and mature T-cell genomic DNA, and provide evidence that rearrangements of the YT35 sequences do occur in the DNA of thymic leukaemia T cells. This suggests that YT35 codes for at least part of the T-cell receptor and that rearrangements occur at this early stage of thymic ontogeny. Furthermore, DNA rearrangements are present in lymphocytes with phenotypic and functional characteristics of helper, killer, or suppressor T cells. We conclude that the three subpopulations of T cells operate via receptor molecules encoded by the same gene family.

Cell Line↗